Mutations

SORL1

SORLA, the sortilin-related receptor with type-A repeats, also known by its gene name SORL1 and as LR11, is an endosomal sorting receptor involved in APP and Aβ trafficking, among other functions. Multiple studies have associated rare, putative loss-of-function variants in SORL1 with an increased risk of Alzheimer’s disease. 

Click here to see key findings from studies demonstrating associations between damaging variants in SORL1 and risk of AD.

There are no consensus guidelines for assigning pathogenicity to SORL1 missense variants. In order to predict the effects of missense variants, Andersen, Holstege, and colleagues focused on organizational features of SORL1 and on proteins with homologous domains to identify positions in SORL1 where amino acid substitutions are most likely to disrupt SORL1 function and increase AD risk. SORL1 is a modular protein, containing multiple functional domains, which are themselves composed of multiple repeating units. Andersen et al. aligned repeated sequences to identify conserved amino acids likely to be important for protein folding or stability. They then identified residues in SORL1 corresponding to the positions of disease-causing variants in homologous domains of other proteins. Based on these considerations, they predicted which residues, when mutated, are moderately or highly likely to have deleterious effects on SORL1 function and increase AD risk. These predictions were validated in a very large data set (Holstege et al., 2023). Click on the buttons below to view the positions assigned by Andersen et al. as highly or moderately likely to increase AD risk if mutated. (Colored circles show positions that have variants curated in the Alzforum database.)

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Search Results

SORL1 (971)

Mutation DNA Change Expected RNA | Protein Consequence Coding/Non-Coding Genomic Region Neuropathology Biological Effect Primary
Papers
c.-2484C>A
Substitution Non-Coding Upstream of 5′ UTR Zhang et al., 2015
c.-1287T>C
(SNP 1)
Substitution Non-Coding Upstream of 5′ UTR Rogaeva et al., 2007
c.-1204G>T
Substitution Non-Coding Upstream of 5′ UTR Zhang et al., 2015
A2G
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
S6T
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
R7T
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
R11P
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown; predicted to be deleterious by SIFT, neutral by Mutation Taster, and benign by PolyPhen-2.

Sassi et al., 2016
G25R
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
C28Y
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
W31Ter (TGG>TAG)
Substitution Substitution | Nonsense Coding Exon 1

Unknown.

Introduces a premature stop codon.

Nicolas et al., 2018
W31Ter (TGG>TGA)
Substitution Substitution | Nonsense Coding Exon 1

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
L35R
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
G38R
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
R46Q
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
G47S
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
G53C
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
D54H
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
P55Rfs
(Pro55Argfs*44, c.164del)
Deletion Deletion | Coding Exon 1

Unknown.

Unknown.

Nicolas et al., 2016
D65Cfs
Deletion Deletion | Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
A66D
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
A69Gfs
Insertion Insertion | Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
A69Rfs
Deletion Deletion | Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
R67S (G>T)
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
R67S (G>C)
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
A69V
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
R71H
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
P76L
Substitution Substitution | Missense Coding Exon 1

Unknown.

Did not affect the maturation (glycosylation) of SORL1 overexpressed in HEK293 cells. Predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Fernández et al., 2016
R79Gfs
Deletion Deletion | Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
P87A
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
K91R
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
V92M
Substitution Substitution | Missense Coding Exon 1

Unknown.

Unknown.

Holstege et al., 2022
c.285+152G>C
(SNP 2)
Substitution Non-Coding Intron 1 Rogaeva et al., 2007
c.285+882T>C
Substitution Non-Coding Intron 1 Webster et al., 2008
c.285+4534G>A
(SNP 3)
Substitution Non-Coding Intron 1 Rogaeva et al., 2007
c.285+4712C>A
Substitution Non-Coding Intron 1 Lee et al., 2007
c.285+5177A>G
Substitution Non-Coding Intron 1 Lin et al., 2017
c.285+5629T>C
(SNP 4)
Substitution Non-Coding Intron 1

Possible effects on SORL1 expression, but findings inconsistent.

Rogaeva et al., 2007
c.285+5716T>C
Substitution Non-Coding Intron 1 Bralten et al., 2011
c.285+6071C>T
Substitution Non-Coding Intron 1 Webster et al., 2008
c.285+6762A>G
Substitution Non-Coding Intron 1 Lin et al., 2017
c.286-5553T>C
Substitution Non-Coding Intron 1 Lin et al., 2017
c.286-4988A>G
Substitution Non-Coding Intron 1 McCarthy et al., 2010
c.286-2723G>A
Substitution Non-Coding Intron 1 Webster et al., 2008
c.286-483C>T
Substitution Non-Coding Intron 1 Webster et al., 2008
N99S
Substitution Substitution | Missense Coding Exon 2

Unknown, but MRI of carrier showed frontotemporal atrophy.

Unknown.

Li et al., 2020
S101F
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
H102Y
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown.

Holstege et al., 2022
N103H
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown.

M105T
Substitution Substitution | Missense Coding Exon 2

Unknown.

Predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2. May introduce a phosphorylation site for the serine/threonine kinase PLK1, per computational modeling.

Sassi et al., 2016
S114R
Substitution Substitution | Missense Coding Exon 2

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Rovelet-Lecrux et al., 2021
S114N
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown.

N115N
Substitution Substitution | Silent Coding Exon 2

Unknown.

Unknown.

Holstege et al., 2017
V116M
Substitution Substitution | Missense Coding exon 2

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
V118M
Substitution Substitution | Missense Coding exon 2

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
R122Ter
(R122X)
Substitution Substitution | Nonsense Coding exon 2

Unknown, but amyloid-PET positive. Global atrophy, superficial siderosis, and subcortical microhemorrhages shown by MRI.

Unknown; predicted to be protein truncating.

Alvarez-Mora et al., 2022
R122G
Substitution Substitution | Missense Coding exon 2

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
S124R (C>A)
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown; predicted to be probably damaging by PolyPhen-2, deleterious by SIFT, and disease causing by Mutation Taster.

Bellenguez et al., 2017
S124R (C>G)
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Nicolas et al., 2016
L127M
Substitution Substitution | Missense Coding Exon 2

Unknown.

Unknown.

c.402+430G>A
Substitution Non-Coding Intron 2 McCarthy et al., 2010
c.402+1255G>A
Substitution Non-Coding Intron 2 McCarthy et al., 2010
c.402+2214T>A
Substitution Non-Coding Intron 2 Bralten et al., 2011
c.402+3452G>-
Deletion Non-Coding Intron 2 Lin et al., 2017
c.403-3C>G
Substitution Non-Coding Intron 2

Unknown.

Holstege et al., 2017
V137G
Substitution Substitution | Missense Coding Exon 3

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
S138F
Substitution Substitution | Missense Coding Exon 3

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
D140N
Substitution Substitution | Missense Coding Exon 3

A carrier clinically diagnosed with Lewy body disease exhibited Alzheimer’s pathology, cerebral amyloid angiopathy, and Lewy body pathology.

Unknown; predicted to be probably damaging by PolyPhen-2, tolerated by SIFT, and disease-causing by Mutation Taster.

Verheijen et al., 2016;
Andersen et al., 2023
Y141C
Substitution Substitution | Missense Coding Exon 3

Unknown.

Unknown; predicted to be probably damaging by PolyPhen-2, deleterious by SIFT, and disease causing by Mutation Taster.

Pottier et al., 2012
K146Q
Substitution Substitution | Missense Coding Exon 3

Unknown.

Unknown; predicted to be benign by PolyPhen-2, tolerated by SIFT, and neutral by Mutation Taster.

Verheijen et al., 2016
P171S
Substitution Substitution | Missense Coding Exon 3

Unknown.

Unknown.

A172V
Substitution Substitution | Missense Coding Exon 3

Unknown.

Unknown; predicted to be damaging by MutationTaster, SIFT, and PolyPhen-2.

Bellenguez et al., 2017
N174del
Deletion Deletion | Deletion Coding Exon 3

Unknown.

Unknown.

Vardarajan et al., 2015
R176W
Substitution Substitution | Missense Coding exon 3

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
c.528+159A>G
(SNP 5)
Substitution Non-Coding Intron 3 Rogaeva et al., 2007
c.528+4125T>G
Substitution Non-Coding Intron 3

Unknown.

Unknown.

Bellenguez et al., 2022
c.529-2562A>G
Substitution Non-Coding Intron 3 Bralten et al., 2011
c.529-1773C>T
Substitution Non-Coding Intron 3 McCarthy et al., 2010
c.529-380G>A
Substitution Non-Coding Intron 3 McCarthy et al., 2010
c.529-2A>G
Substitution Non-Coding Intron 3

Unknown.

Unknown; predicted to be deleterious by Mutation Taster.

Campion et al., 2019
A180P
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
A182T
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown.

F191S
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown; predicted to be tolerated by SIFT, neutral by Mutation Taster, and benign by PolyPhen-2.

Holstege et al., 2017
R205Q
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown; predicted to be possibly damaging by PolyPhen-2, tolerated by SIFT, and disease causing by Mutation Taster.

Verheijen et al., 2016
L219P
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
R224G
Substitution Substitution | Missense Coding Exon 4 Holstege et al., 2022
R224T
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
Q230R
Substitution Substitution | Missense Coding Exon 4

Unknown.

Unknown.

c.690+363T>C
Substitution Non-Coding Intron 4 Webster et al., 2008
K233R
Substitution Substitution | Missense Coding Exon 5

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
D236G
Substitution Substitution | Missense Coding Exon 5

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
E246Dfs
Deletion Deletion | Coding Exon 5 Holstege et al., 2022
c.758+65T>A
(SNP 6)
Substitution Non-Coding Intron 5 Rogaeva et al., 2007
c.758+196G>A
Substitution Non-Coding Intron 5 Webster et al., 2008
c.758+1497G>A
Substitution Non-Coding Intron 5 Webster et al., 2008
c.758+3184A>G
Substitution Non-Coding Intron 5 Webster et al., 2008
c.759-2763A>C
Substitution Non-Coding Intron 5 Reynolds et al., 2013
c.759-2615A>G
Substitution Non-Coding Intron 5 Lin et al., 2017
c.759-1888T>C
Substitution Non-Coding Intron 5 Lin et al., 2017
c.759-1858G>T
Substitution Non-Coding Intron 5 Reynolds et al., 2013
c.759-2del
Deletion Non-Coding Intron 5

Unknown.

Unknown.

Holstege et al., 2022
N262S
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
I266V
Substitution Substitution | Missense Coding Exon 6

Unknown; predicted to be tolerated.

Holstege et al., 2022;
Andersen et al., 2023
R268Ter
(R268X)
Substitution Substitution | Nonsense Coding Exon 6

Unknown.

Unknown; predicted to be disease-causing by Mutation Taster.

Nicolas et al., 2016
H269H
(SNP 7)
Substitution Substitution | Silent Coding Exon 6

Some carriers had autopsy-confirmed AD.

Predicted tolerated in silico. Levels of wild-type and H269H transcripts were similar in prefrontal cortices from AD donors, suggesting that this variant does not alter expression of SORL1.

Rogaeva et al., 2007
E270K
Substitution Substitution | Missense Coding Exon 6

Unknown.

Reduced binding affinity to APP, compared with wild-type SORL1, resulting in more APP at the cell surface and increased secretion of Aβ40, Aβ42, sAPPα and sAPPβ. Enlarged endosomes.

Vardarajan et al., 2015
Y274H
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
V277L
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown.

Andersen et al., 2023
R279Ter
(R279X)
Substitution Substitution | Nonsense Coding Exon 6

Autopsy-confirmed Alzheimer’s disease (Braak stage 6) in one carrier.

Introduces a premature stop codon; predicted to be disease-causing by Mutation Taster.

Raghavan et al., 2018
R279L
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown.

D282N
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019;
Andersen et al., 2023
F283L
Substitution Substitution | Missense Coding Exon 6

Unkonwn.

Unkonwn.

Holstege et al., 2022
F284V
Substitution Substitution | Missense Coding Exon 6

Unkonwn.

Unkonwn.

Holstege et al., 2022
R287W
Substitution Substitution | Missense Coding Exon 6

Unkonwn.

Unkonwn.

Holstege et al., 2022
R287Q
Substitution Substitution | Missense Coding Exon 6

Unkonwn.

Unkonwn.

L294F
Substitution Substitution | Missense Coding Exon 6

Unkonwn.

Unkonwn.

Holstege et al., 2022
V297M
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown; predicted to be disease-causing by Mutation Taster, probably damaging by PolyPhen-2, damaging by SIFT, and neutral by PROVEAN.

El Bitar et al., 2019
R303W
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Fernández et al., 2016
M307V
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown.

Verheijen et al., 2016;
Andersen et al., 2023
M307R
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown.

Andersen et al., 2023
V312A
Substitution Substitution | Missense Coding Exon 6

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
c.939+163C>T
(SNP 8)
Substitution Non-Coding Intron 6

Does not affect SORL1 protein levels in brains of AD subjects but may affect SORL1 expression in response to BDNF.

Rogaeva et al., 2007
c.939+405A>G
Substitution Non-Coding Intron 6 Bralten et al., 2011
c.939+1492A>G
Substitution Non-Coding Intron 6 Webster et al., 2008
c.939+2958C>T
Substitution Non-Coding Intron 6 Yin et al., 2016
c.939+3362G>A
(SNP 9)
Substitution Non-Coding Intron 6

Reported to affect SORL1 expression in brains of young people but not AD patients; affected SORL1 expression in response to BDNF in hIPSC-derived neurons from AD cases.

Rogaeva et al., 2007
c.940-7761A>G
Substitution Non-Coding Intron 6 Wen et al., 2013
c.940-6917C>T
Substitution Non-Coding Intron 6 Reynolds et al., 2013
c.940-2747C>T
(SNP 10)
Substitution Non-Coding Intron 6

No effect on SORL1 protein levels in AD brains, but affected SORL1 expression in response to BDNF in hIPSC-derived neurons from AD cases.

Rogaeva et al., 2007
c.940-841A>G
Substitution Non-Coding Intron 6 Webster et al., 2008
H314Y
Substitution Substitution | Missense Coding Exon 7

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
H314L
Substitution Substitution | Missense Coding Exon 7

Unknown.

Unknown; predicted tolerated in silico.

Holstege et al., 2017
L316F
Substitution Substitution | Missense Coding Exon 7

Unknown.

Unknown.

V324L
Substitution Substitution | Missense Coding Exon 7

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2.

Verheijen et al., 2016
R332W
Substitution Substitution | Missense Coding Exon 7

Unknown.

Impairs maturation (glycosylation) of SORL1 and trafficking to the plasma membrane, accompanied by increased release of Aβ.

Nicolas et al., 2016
H344P
Substitution Substitution | Missense Coding Exon 7

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
c.1041+34A>G
Substitution Non-Coding Intron 7 Holstege et al., 2017
Y350Ter
(Y350fs*)
Deletion Deletion | Coding Exon 8

Unknown.

Unknown.

Verheijen et al., 2016
I351V
Substitution Substitution | Missense Coding Exon 8 Holstege et al., 2022
I351I
Substitution Substitution | Nonsense Coding Exon 8

Unknown.

Unknown.

Holstege et al., 2017
A352T
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

S355S
Substitution Substitution | Silent Coding Exon 8

Unknown.

Unknown.

Holstege et al., 2017
V361Cfs
(V361fs)
Duplication Duplication | Coding Exon 8

Unknown.

Unknown.

Campion et al., 2019
V361L
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown; predicted to be deleterious by PolyPhen-2 and Mutation Taster, but likely benign by Mendelian Clinically Applicable Pathogenicity.

Sun et al., 2021;
Andersen et al., 2023
N367D
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
N368S
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

Holstege et al., 2022
R369C
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

Holstege et al., 2022
R369H
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

Holstege et al., 2022
N371D
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

N371S
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

N371T
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Vardarajan et al., 2015
A377T
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown.

G379W
Substitution Substitution | Missense Coding Exon 8

Unknown, but MRI of two carriers diagnosed with AD showed hippocampal and cortical atrophy.

Unknown; predicted to be deleterious.

Xiromerisiou et al., 2021;
Andersen et al., 2023
F382L
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown; predicted to be deleterious.

Holstege et al., 2022;
Andersen et al., 2023
V389M
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
Y391C
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown, but predicted to be deleterious

Fernández et al., 2016
G398C
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown, but predicted to be deleterious.

Holstege et al., 2022;
Andersen et al., 2023
G398S
Substitution Substitution | Missense Coding Exon 8

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
c.1211+2T>G
Substitution Non-Coding Intron 8

Unknown.

Ex vivo splicing assays confirmed in silico predictions that this variant affects splicing, generating aberrant transcripts containing premature stop codons.

Nicolas et al., 2016
c.1212-1864T>G
(SNP 11)
Substitution Non-Coding Intron 8

Did not associate with levels of SORL1 transcripts in cortices of neurologically normal individuals.

Rogaeva et al., 2007
P410T
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
P410L
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
H415Q
Substitution Substitution | Missense Coding Exon 9 Holstege et al., 2022
R416G
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Fernández et al., 2016
R416Ter
(R416X)
Substitution Substitution | Nonsense Coding Exon 9

Unknown.

Introduces a premature stop codon; predicted to be disease-causing by Mutation Taster.

Verheijen et al., 2016
R416Q
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Sassi et al., 2016
R416L
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown.

Holstege et al., 2022
E418Ter
Substitution Substitution | Nonsense Coding Exon 9

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
I425V
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown, but predicted to be tolerated.

Holstege et al., 2022;
Andersen et al., 2023
L428P
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown.

Holstege et al., 2022
G447Rfs
(G447Rfs*22)
Duplication Duplication | Coding Exon 9

Unknown.

Reduced levels of SORL1 mRNA, measured in lymphoblast cells from the carrier of this variant.

Verheijen et al., 2016
G448E
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown.

Holstege et al., 2022
A455G
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown.

Holstege et al., 2022
T459K
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted to be tolerated by SIFT but deleterious by Mutation Taster and PolyPhen-2.

Fernández et al., 2016
T459M
Substitution Substitution | Missense Coding Exon 9 Holstege et al., 2022
N466D
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
C467Y
Substitution Substitution | Missense Coding Exon 9

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
c.1404+5T>C
Substitution Non-Coding Intron 9 Holstege et al., 2017
c.1405-69C>T
(SNP 12)
Substitution Non-Coding Intron 9 Rogaeva et al., 2007
C473S
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted to be deleterious.

Nicolas et al., 2016;
Andersen et al., 2023
S474C
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted to be deleterious.

Holstege et al., 2017;
Andersen et al., 2023
H476R
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown.

Holstege et al., 2022
R480C
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted to be deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
R480P
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Sassi et al., 2016
N486S
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown.

Q488Ter
Substitution Substitution | Nonsense Coding Exon 10

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
R490W
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
R490Q
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Fernández et al., 2016
I494F
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
S499W
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown.

Holstege et al., 2022
S499L
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown.

Holstege et al., 2022
L503I
Substitution Substitution | Missense Coding Exon 10

Unknown.

Unknown.

Holstege et al., 2022
G508S
Substitution Substitution | Missense Coding Exon 10/11

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
c.1523-47C>A
Substitution Non-Coding Intron 10 Holstege et al., 2017
c.1523-29T>G
Substitution Non-Coding Intron 10 Holstege et al., 2017
S509Ter
Substitution | Nonsense Non-Coding Exon 11

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
G511R
Substitution Substitution | Missense Coding Exon 11

Unknown.

Abolished binding of Aβ to the SORL1 VPS10P domain and slowed the intracellular breakdown of Aβ. Resulted in enlarged endosomes and increased secretion of Aβ40, Aβ42.

Pottier et al., 2012
K512N
Substitution Substitution | Missense Coding Exon 11

Unknown.

Unknown.

Holstege et al., 2022
N513S
Substitution Substitution | Missense Coding Exon 11

Unknown.

Unknown.

L514V
Substitution Substitution | Missense Coding Exon 11

Unknown.

Unknown.

Holstege et al., 2022
S516N
Substitution Substitution | Missense Coding Exon 11

Unknown.

Unknown.

Lin et al., 2017
V520M
Substitution Substitution | Missense Coding Exon 11

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019;
Andersen et al., 2023
A528T
(SNP 13)
Substitution Substitution | Missense Coding Exon 11

Unknown.

Reduced binding to APP, compared with wild-type SORL1, when expressed in HEK293 cells. In microglia-like cells derived from human ESCs, the A528T mutation led to an accumulation of cell-surface and early endosomal proteins, increased levels of APOE, and APOE-isoform-dependent effects on Aβ phagocytosis.

Rogaeva et al., 2007
c.1596+16C>T
Substitution Non-Coding Intron 11 Holstege et al., 2017
c.1596+589C>T
Substitution Non-Coding Intron 11 Lin et al., 2017
c.1596+3740T>C
Substitution Non-Coding Intron 11 Reynolds et al., 2013
c.1597-4663T>G
Substitution Non-Coding Intron 11 Bralten et al., 2011
c.1597-4595G>A
Substitution Non-Coding Intron 11 Bralten et al., 2011
c.1597-2411C>T
Substitution Non-Coding Intron 11 Bralten et al., 2011
G543E
Substitution Substitution | Missense Coding Exon 12

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Nicolas et al., 2016
D544G
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown.

H545D
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown.

Holstege et al., 2022
G546V
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
A551A
Substitution Substitution | Silent Coding Exon 12

Unknown.

Unknown; predicted tolerated in silico.

El Bitar et al., 2019
I552V
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown; predicted to be tolerated by SIFT and benign by PolyPhen-2, but deleterious by Mutation Taster.

Holstege et al., 2017
I552S
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown.

Holstege et al., 2022
Q554E
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown.

G555R
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown.

Holstege et al., 2022
M556V
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
T558S
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
N559S
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown; predicted in silico to be tolerated.

Sassi et al., 2016
E560K
Substitution Substitution | Missense Coding Exon 12

Unknown.

Unknown; predicted in silico to be tolerated.

Verheijen et al., 2016
c.1685+1290T>C
Substitution Non-Coding Intron 12 Webster et al., 2008
c.1685+3447T>C
(SNP 14)
Substitution Non-Coding Intron 12 Rogaeva et al., 2007
c.1685+4694T>C
Substitution Non-Coding Intron 12 Reynolds et al., 2013
c.1686-3216A>G
Substitution Non-Coding Intron 12 Lin et al., 2017
c.1686-1992A>G
Substitution Non-Coding Intron 12 Lin et al., 2017
c.1686-222C>T
Substitution Non-Coding Intron 12 Lin et al., 2017
c.1686-28A>T
Substitution Non-Coding Intron 12 Holstege et al., 2017
S564G
Substitution Substitution | Missense Coding Exon 13

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Rovelet-Lecrux et al., 2021;
Andersen et al., 2023
N566S
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Andersen et al., 2023
T570I
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown; predicted to be deleterious.

Holstege et al., 2022;
Andersen et al., 2023
F574L
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
S577P
Substitution Substitution | Missense Coding Exon 13

Unknown.

Impaired maturation (glycosylation) of SORL1 overexpressed in HEK293 cells or expressed at endogenous levels in human iPSCs.

Verheijen et al., 2016
V581G
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2

Holstege et al., 2017
V583M
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown, but substitution of the hydrophobic valine residue with a hydrophobic methionine is predicted to be tolerated.

Holstege et al., 2022;
Andersen et al., 2023
V583L
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown, but substitution of the hydrophobic valine residue with a hydrophobic leucine is predicted to be tolerated.

Fernández et al., 2016;
Andersen et al., 2023
V583V
Substitution Substitution | Nonsense Coding Exon 13

Unknown.

Unknown.

Holstege et al., 2017
G585D
Substitution Substitution | Missense Coding Exon 13 Holstege et al., 2022
T588I
Substitution Substitution | Missense Coding Exon 13

Unknown.

More APP at the cell surface and elevated levels of Aβ42, sAPPα, and sAPPβ in the media of cells expressing the T588I variant, compared with cells expressing wild-type SORL1.

Cuccaro et al., 2016
E589G
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

E592K
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Holstege et al., 2022
T595I
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Holstege et al., 2022
I599V
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Holstege et al., 2022
S602L
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Nicolas et al., 2018
E605D
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
V607F
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
Q614H
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Fernández et al., 2016
V615F
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
A617V
Substitution Substitution | Missense Coding Exon 13

Unknown.

Unknown.

Holstege et al., 2022
c.1864+21A>C
Substitution Non-Coding Intron 13 Lin et al., 2017
c.1864+41G>T
(SNP 15)
Substitution Non-Coding Intron 13

Did not associate with levels of SORL1 protein in AD brains.

Rogaeva et al., 2007
c.1865-640C>T
Substitution Non-Coding Intron 13 Webster et al., 2008
c.1865-2A>C
Substitution Non-Coding intron 13

Unknown.

Unknown; predicted to be deleterious by Mutation Taster.

Campion et al., 2019
V623A
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
S636T
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be tolerated by SIFT but deleterious by Mutation Taster and PolyPhen-2.

Verheijen et al., 2016
R639G
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

R639W
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

Holstege et al., 2022
R639Q
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2.

Verheijen et al., 2016
R639L
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

Holstege et al., 2022
E642K
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2.

Verheijen et al., 2016
E642A
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
H647Tfs
(p.(Gly646fs))
Deletion Deletion | Coding Exon 14

Unknown.

This single-nucleotide deletion results in a frameshift.

Nicolas et al., 2016
R653Q
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
R654W
Substitution Substitution | Missense Coding Exon 14

Unknown.

Impairs maturation (glycosylation) of SORL1 and trafficking to the plasma membrane.

Nicolas et al., 2016
R654Q
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

Holstege et al., 2022
P656S
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

T659Sfs
(T659Sfs*30)
Deletion Deletion | Coding Exon 14

Unknown.

Unknown.

Verheijen et al., 2016
P656R
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

T659A
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

C660Afs
Deletion Deletion | Coding Exon 14

Unknown.

Unknown.

Holstege et al., 2022
N662S
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

Holstege et al., 2022
P669L
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Fernández et al., 2016
V670A
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
V672M
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown.

Holstege et al., 2022
N674S
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be deleterious by PolyPhen-2 and Mutation Taster, but tolerated by SIFT.

Verheijen et al., 2016
R679W
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Fernández et al., 2016
R679Q
Substitution Substitution | Missense Coding Exon 14

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Holstege et al., 2017
c.2051+49A>C
Substitution Non-Coding Intron 14 Bralten et al., 2011
c.2051+690T>G
Substitution Non-Coding Intron 14 Bralten et al., 2011
c.2051+986G>A
Substitution Non-Coding Intron 14 Bralten et al., 2011
G687S
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown.

Fernández et al., 2016
K689Q
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
S695S
Substitution Substitution | Nonsense Coding Exon 15

Unknown.

Unknown.

Holstege et al., 2017
V700A
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown.

P703L
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown.

Holstege et al., 2022
P712Lfs
Deletion Deletion | Coding Exon 15

Unknown.

This single-nucleotide deletion results in a frameshift.

Holstege et al., 2022
P712T
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown.

C716W
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
V718M
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown.

Holstege et al., 2022
G719V
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
Y722C
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
T725K
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
T725M
Substitution Substitution | Missense Coding Exon 15

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Sassi et al., 2016
c.2180+29G>C
Substitution Non-Coding Intron 15

Unknown.

Unknown.

Holstege et al., 2017
c.2181-10G>A
Substitution Non-Coding Intron 15

Unknown.

Unknown.

Holstege et al., 2022
R729W
Substitution Substitution | Missense Coding Exon 16

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Nicolas et al., 2016
R729Q
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Holstege et al., 2017
D734N
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
C736Y
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted to be deleterious.

Nicolas et al., 2018;
Andersen et al., 2023
G738Ter
Substitution Substitution | Nonsense Coding Exon 16

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
G738R (G>C)
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
G738R (G>A)
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
D740E
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown.

Holstege et al., 2022
A743V
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
R744Ter
(R744X)
Substitution Substitution | Nonsense Coding Exon 16

Unknown.

Microglia-like cells derived from human embryonic stem cells made homozygous for the R744Ter mutation lacked SORL1.

Holstege et al., 2017
R744Q
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown.

E748D
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown.

V750I
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted to be tolerated by SIFT, neutral by Mutation Taster, and probably damaging by PolyPhen-2.

Verheijen et al., 2016
P751S
Substitution Substitution | Missense Coding Exon 16

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
C752Sfs
(C752Sfs*22)
Deletion Deletion | Coding Exon 16

Unknown.

This two-nucleotide deletion results in a frameshift and the introduction of a premature stop codon.

Verheijen et al., 2016
c.2266+590A>C
Substitution Non-Coding Intron 16 Bralten et al., 2011
c.2267-1094C>T
Substitution Non-Coding Intron 16 Lin et al., 2017
c.2267-1006G>A
Substitution Non-Coding Intron 16 Reitz et al., 2013
E759K
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
L762P
Substitution Substitution | Missense Coding Exon 17

Carrier had autopsy-confirmed AD; amyloid plaques, neurofibrillary tangles, gliosis, and prominent neuron loss in cortex, hippocampus, and amygdala.

Unknown; predicted deleterious in silico.

Verheijen et al., 2016
A764A
Substitution Substitution | Nonsense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2017
V765L
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2022
R771C
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
L774R
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2022
S776L
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
E780Sfs
Deletion Deletion | Coding Exon 17

Unknown.

This single-nucleotide deletion results in a frame shift.

Holstege et al., 2022
T779T
Substitution Substitution | Silent Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2017
E780K
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2022
P783L
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

G786R
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Holstege et al., 2017
R788W
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted deleterious in silico.

Rovelet-Lecrux et al., 2021
A789V
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2022
L793R
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
H799Y
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
W804Ter
(W804X)
Substitution Substitution | Nonsense Coding Exon 17

Introduces a premature stop codon.

Schramm et al., 2022
W804C
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
S805S
Substitution Substitution | Nonsense Coding Exon 17

Unknown.

Unknown.

Nicolas et al., 2018
D806N
Substitution Substitution | Missense Coding Exon 17

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Nicolas et al., 2016
L807P
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown; predicted deleterious in silico.

Verheijen et al., 2016
V811I
Substitution Substitution | Missense Coding Exon 17

Unknown.

Unknown.

Holstege et al., 2022
c.2439+64G>A
Substitution Non-Coding Intron 17 Reitz et al., 2013
c.2440-15C>T
Substitution Non-Coding Intron 17 Holstege et al., 2017
R814C
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
R814H
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted deleterious.

Fernández et al., 2016;
Andersen et al., 2023
L815F
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown.

Holstege et al., 2022
N818K (T>A)
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
N818K (T>G)
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
Q823Ter
(Q823X)
Substitution Substitution | Nonsense Coding Exon 18

Unknown.

Introduces a premature stop codon.

Schramm et al., 2022
E824Q
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown.

V825V
Substitution Substitution | Silent Coding Exon 18

Unknown.

Unknown.

Nicolas et al., 2018
N828S
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted tolerated in silico.

Sassi et al., 2016
G830D
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
T833T
(SNP 16)
Substitution Substitution | Silent Coding Exon 18

Unknown.

Unknown.

Rogaeva et al., 2007
V834A
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown.

Holstege et al., 2022
A838T
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
L845R
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
W848Ter
(W848X)
Substitution Substitution | Nonsense Coding Exon 18

Unknown.

Introduces a premature stop codon.

Gómez-Tortosa et al., 2018
D850Qfs
Deletion Deletion | Coding Exon 18

Unknown.

This four-nucleotide deletion results in a frame shift.

Campion et al., 2019
D850V
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
G852R
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
G852A
Substitution Substitution | Missense Coding Exon 18

Unknown.

Unknown.

Gómez-Tortosa et al., 2018
c.2571+15G>A
Substitution Non-Coding Intron 18 Reitz et al., 2013
c.2571+180T>G
(SNP 17)
Substitution Non-Coding Intron 18 Rogaeva et al., 2007
c.2571+843T>A
Substitution Non-Coding Intron 18 Webster et al., 2008
D862G
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown.

Holstege et al., 2022
R866Ter
(R866X)
Substitution Substitution | Nonsense Coding Exon 19

Unknown.

Introduces a premature stop codon.

Raghavan et al., 2018
T868Kfs
Deletion Deletion | Coding Exon 19

Unknown.

This deletion, resulting in a frame shift, is predicted to be protein truncating.

Nicolas et al., 2016
I869V
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown; predicted to be tolerated.

Holstege et al., 2022;
Andersen et al., 2023
V870I
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown.

Verheijen et al., 2016;
Andersen et al., 2023
R877C
Substitution Substitution | Missense Coding Exon 19

Unknown.

Predicted to be damaging by SIFT, Mutation Taster, and PolyPhen-2.

Rovelet-Lecrux et al., 2021
V882I
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
L883F
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
V884M
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
P885T
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Verheijen et al., 2016
E887G
Substitution Substitution | Missense Coding Exon 19

Unknown.

Unknown; predicted to be benign by PolyPhen-2, but deleterious by SIFT.

Vardarajan et al., 2015
c.2664-521A>G
Substitution Non-Coding Intron 19 Lin et al., 2017
M890V
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
M890I
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
T893R
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
P900S
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
R904W
Substitution Substitution | Missense Coding Exon 20

Amyloid plaques, neurofibrillary tangles, limited CAA.

Unknown; predicted deleterious in silico.

Tejada Moreno et al., 2022
R904Q
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
M907V
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Holstege et al., 2022
S910F
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
N924S
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious.

Pottier et al., 2012;
Andersen et al., 2023
D929Y
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
D929D
Substitution Substitution | Nonsense Coding Exon 20

Unknown.

Unknown.

Holstege et al., 2017
D930N
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
W932Ter
(W932X)
Substitution Substitution | Nonsense Coding Exon 20 Schramm et al., 2022
W932C
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Holstege et al., 2022
I933T
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
Y934C
Substitution Substitution | Missense Coding Exon 20

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Rovelet-Lecrux et al., 2021;
Andersen et al., 2023
T936M
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
C942G
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Verheijen et al., 2016
I943V
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
R945W
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
R945Q
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

I946V
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
T947M
Substitution Substitution | Missense Coding Exon 20

Unknown.

Impairs SORL1 trafficking to the cell surface and weakens SORL1’s interaction with the EphA4 receptor tyrosine kinase.

Vardarajan et al., 2015
R953C
Substitution Substitution | Missense Coding Exon 20

Amyloid plaques, neurofibrillary tangles, and TDP-43 inclusions.

Impairs maturation (glycosylation) and disrupts trafficking of SORL1.

Fazeli et al., 2023
R953H
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

Holstege et al., 2022
L957P
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
N959K
Substitution Substitution | Missense Coding Exon 20

Unknown.

Unknown.

P961Rfs
Deletion Deletion | Coding Exon 20

Unknown.

This single-nucleotide deletion introduces a frame shift.

Holstege et al., 2022
H962Afs
Duplication Duplication | Coding Exon 20

Unknown.

This single-nucleotide insertion introduces a frame shift.

H962Pfs
(H962Pfs*45)
Deletion Deletion | Coding Exon 20

Unknown.

Compared with iPSC-derived neurons from a control subject, cells from the mutation carrier expressed half the amount of SORL1 protein and exhibited enlarged endosomes.

Holstege et al., 2017
c.2911-39C>T
Substitution Non-Coding Intron 20 Holstege et al., 2017
Q980R
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Verheijen et al., 2016
Q980L
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown.

Holstege et al., 2022
I983Yfs
Deletion Deletion | Coding Exon 21

Unknown.

This single-nucleotide deletion results in a frame shift.

F984L
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown.

R985Ter
(R985X)
Substitution Substitution | Nonsense Coding Exon 21

Unknown.

Unknown.

Fernández et al., 2016
A986T
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Rovelet-Lecrux et al., 2021
M994L
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown.

E995G
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
N999D
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown; predicted tolerated in silico.

Rovelet-Lecrux et al., 2021
G1003Hfs
(G1003Hfs*37)
Duplication Duplication | Coding Exon 21

Unknown.

This four-nucleotide insertion results in a frameshift and the introduction of a premature stop codon.

Holstege et al., 2017
T1002M
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
M1005I
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown.

G1013R
Substitution Substitution | Missense Coding Exon 21

Unknown.

Unknown.

c.3049+988A>T
(SNP 18)
Substitution Non-Coding Intron 21 Rogaeva et al., 2007
c.3049+1921C>A
Substitution Non-Coding Intron 21 Liu et al., 2017
c.3049+2117G>C
Substitution Non-Coding Intron 21 Bralten et al., 2011
c.3049+3427T>C
Substitution Non-Coding Intron 21 Reitz et al., 2013
c.3050-3221T>C
Substitution Non-Coding Intron 21 Bralten et al., 2011
c.3050-3093C>T
Substitution Non-Coding Intron 21 Webster et al., 2008
c.3050-2179G>A
Substitution Non-Coding Intron 21
c.3050-2062T>C
Substitution Non-Coding Intron 21 Webster et al., 2008
c.3050-1379G>T
Substitution Non-Coding Intron 21
c.3050-382A>T
Substitution Non-Coding Intron 21 Lin et al., 2017
c.3050-96G>A
Substitution Non-Coding Intron 21

Unknown.

Unknown.

Holstege et al., 2022
c.3050-78A>G
Substitution Non-Coding Intron 21 Lin et al., 2017
G1017_E1074del
(c.3050-2A > G)
Substitution | Deletion Non-Coding Intron 21

Unknown.

Causes exon 22 skipping. At the protein level, the mutation is expected to result in an in-frame deletion of amino acids 1017–1074, which would completely remove the epidermal growth factor-like domain of SORL1.

Thonberg et al., 2017
N1019S
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown.

A1020V
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
V1022L
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown.

Holstege et al., 2022
C1026R
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
L1028V
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown.

C1030Sfs
Deletion Deletion | Coding Exon 22

Unknown.

This single-nucleotide deletion results in a frame shift.

N1035S
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
R1041M
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown.

Holstege et al., 2022
R1041S
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown; predicted tolerated in silico.

Vardarajan et al., 2015
S1048N
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
D1055E
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown.

Y1064C
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
Q1074E
Substitution Substitution | Missense Coding Exon 22

Unknown.

Unknown; predicted tolerated in silico.

Vardarajan et al., 2015
c.3223+1359G>A
Substitution Non-Coding Intron 22 Webster et al., 2008
c.3224-1201T>C
Substitution Non-Coding Intron 22 Reitz et al., 2013
N1076S
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown.

T1077N
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
R1080C
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted deleterious.

Fernández et al., 2016;
Andersen et al., 2023
R1080H
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
N1081N
Substitution Substitution | Silent Coding Exon 23

Unknown.

Unknown.

Holstege et al., 2017
R1084C
Substitution Substitution | Missense Coding Exon 23

Unknown.

Predicted deleterious. Structural modeling suggests a change in secondary structure and misfolding of the protein.

El Bitar et al., 2019
R1084H
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Verheijen et al., 2016
I1091V
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown.

Sassi et al., 2016;
Andersen et al., 2023
S1093G
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown.

I1094V
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Holstege et al., 2017
W1095C
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted deleterious.

Rovelet-Lecrux et al., 2021;
Andersen et al., 2023
W1096G
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown.

Holstege et al., 2022
F1099L
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted to be tolerated by SIFT and benign by PolyPhen-2, but disease-causing by Mutation Taster.

Vardarajan et al., 2015
D1100N
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown

El Bitar et al., 2019;
Andersen et al., 2023
C1103Vfs
(C1103Vfs*4)
Deletion Deletion | Coding Exon 23

Unknown.

Single-nucleotide deletion resulting in a frameshift and the introduction of a premature stop codon.

Verheijen et al., 2016
G1104R
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown.

D1105H
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2017;
Andersen et al., 2023
M1106L
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
D1108N
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
C1112Y
Substitution Substitution | Missense Coding Exon 23

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
P1113S
Substitution Substitution | Missense Coding Exon 23-24

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Verheijen et al., 2016
P1113A
Substitution Substitution | Missense Coding Exon 23-24

Unknown.

Unknown.

c.3337+1G>A
Substitution Non-Coding Intron 23

Unknown.

This variant affects a splice-donor site.

c.3337+10C>T
Substitution Non-Coding Intron 23 Holstege et al., 2017
c.3337+541A>G
Substitution Non-Coding Intron 23 Webster et al., 2008
c.3337+1210A>G
Substitution Non-Coding Intron 23 Webster et al., 2008
c.3337+1640A>G
Substitution Non-Coding Intron 23 Bralten et al., 2011
c.3338-1913G>A
Substitution Non-Coding Intron 23 Bralten et al., 2011
I1116V
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted tolerated in silico.

Vardarajan et al., 2015
D1120Y
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
F1123L
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
R1124C
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
R1124S
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
Q1126R
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
P1133L
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown.

Holstege et al., 2022
Y1136C
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown.

E1141G
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
D1142Y
Substitution Substitution | Missense Coding Exon 24
D1146N
Substitution Substitution | Missense Coding Exon 24

Unknown.

Predicted deleterious.

Rovelet-Lecrux et al., 2021;
Andersen et al., 2023
S1148R
Substitution Substitution | Missense Coding Exon 24

Unknown.

Unknown.

Holstege et al., 2023;
Andersen et al., 2023
c.3460+12T>C
Substitution Non-Coding Intron 24 Holstege et al., 2017
c.3460+13C>T
Substitution Non-Coding Intron 24 Holstege et al., 2017
c.3460+202C>T
Substitution Non-Coding Intron 24 Liu et al., 2017
c.3460+868A>G
Substitution Non-Coding Intron 24 Bralten et al., 2011
c.3460+987C>A
Substitution Non-Coding Intron 24 Bralten et al., 2011
c.3461-1442T>C
Substitution Non-Coding Intron 24 Webster et al., 2008
c.3461-1177C>G
Substitution Non-Coding Intron 24 Lin et al., 2017
c.3461-979C>T
Substitution Non-Coding Intron 24 Liu et al., 2017
c.3461-897C>T
Substitution Non-Coding Intron 24 Lin et al., 2017
c.3461-802T>C
Substitution Non-Coding Intron 24 Liu et al., 2017
c.3461-419G>A
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-401C>T
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-360T>G
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-357A>G
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-320T>G
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-317C>G
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-303A>G
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-275G>A
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
c.3461-142G>A
Substitution Non-Coding Intron 24

Unknown.

Unknown.

Holstege et al., 2022
H1156H
Substitution Substitution | Silent Coding Exon 25

Unknown.

Unknown.

Holstege et al., 2017
Q1157R
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown.

R1159W
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
D1161E
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
S1167Y
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
S1167S
Substitution Substitution | Nonsense Coding Exon 25

Unknown.

Unknown.

Holstege et al., 2017
G1168V
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
M1169I
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown.

Holstege et al., 2022
I1171V
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown.

R1172C
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
R1172H
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
C1177Y
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
N1181N
Substitution Substitution | Silent Coding Exon 25

Unknown.

Unknown.

Holstege et al., 2017
D1182N
Substitution Substitution | Missense Coding Exon 25

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
S1187S
(SNP 19)
Substitution Substitution | Silent Coding Exon 25

Unknown, but associated with functional connectivity in an imaging study of Chinese subjects.

Predicted tolerated in silico. Might influence SORL1 expression in a region- and disease-dependent manner.

Rogaeva et al., 2007
C1192Y
Substitution Substitution | Missense Coding Exon 25

Unknown, but MRI of carrier showed whole-brain atrophy that was particularly prominent in the medial temporal lobes and hippocampi.

Unknown; predicted deleterious.

Cao et al., 2021;
Andersen et al., 2023
A1194T
Substitution Substitution | Missense Coding Exon 25/26

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
c.3580+2T>C
Substitution Non-Coding Intron 25

Unknown.

Unknown.

c.3580+2T>A
Substitution Non-Coding Intron 25

Unknown.

Unknown.

Holstege et al., 2022
c.3580+74C>G
(SNP 20)
Substitution Non-Coding Intron 25 Rogaeva et al., 2007
c.3580+145G>A
Substitution Non-Coding Intron 25 Reitz et al., 2013
c.3580+229G>A
Substitution Non-Coding Intron 25 Bralten et al., 2011
c.3580+2223G>A
Substitution Non-Coding Intron 25 Lin et al., 2017
c.3581-2615G>A
Substitution Non-Coding Intron 25 Liu et al., 2017
c.3581-2354T>G
Substitution Non-Coding Intron 25 Liu et al., 2017
c.3581-2241T>C
Substitution Non-Coding Intron 25 Webster et al., 2008
c.3581-2227C>T
Substitution Non-Coding Intron 25 Webster et al., 2008
c.3581-2189C>G
Substitution Non-Coding Intron 25 Marioni et al., 2018
c.3581-2133A>G
Substitution Non-Coding Intron 25 Webster et al., 2008
c.3581-1516T>A
Substitution Non-Coding Intron 25 Webster et al., 2008
c.3581-650T>G
Substitution Non-Coding Intron 25 Reitz et al., 2013
c.3581-460C>T
Substitution Non-Coding Intron 25 Bralten et al., 2011
c.3581-26G>A
Substitution Non-Coding Intron 25 Holstege et al., 2017
c.3581-18C>G
(SNP 21)
Substitution Non-Coding Intron 25 Rogaeva et al., 2007
c.3581-1G>T
Substitution Non-Coding Intron 25 Fernández et al., 2016
Y1196C
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
A1201S
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown.

R1207Ter
(R1207X)
Substitution Substitution | Nonsense Coding Exon 26

Unknown.

Unknown; predicted deleterious in silico.

Sassi et al., 2016
R1207Q
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted tolerated in silico.

Vardarajan et al., 2015
G1209R
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
P1213S
Substitution Substitution | Missense Coding Exon 26

Unknown, but MRI of carrier showed mild brain atrophy.

Predicted to be deleterious by Mutation Taster, Polyphen-2, and PROVEAN, but tolerated by SIFT. In silico modeling showed a change in protein folding and secondary structure.

El Bitar et al., 2019
W1216Ter
(W1216X)
Substitution Substitution | Nonsense Coding Exon 26

Unknown.

Unknown.

Nicolas et al., 2016
D1219G
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted deleterious.

Nicolas et al., 2016;
Andersen et al., 2023
G1220R
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted deleterious.

Bellenguez et al., 2017
D1221Y
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown.

T1222M
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted tolerated in silico.

Holstege et al., 2017
T1222T
Substitution Substitution | Nonsense Coding Exon 26

Unknown.

Unknown.

Holstege et al., 2017
C1224Y
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
P1232A
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown.

Holstege et al., 2022
V1233G
Substitution Substitution | Missense Coding Exon 26

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral by Mutation Taster and benign by PolyPhen-2.

Sassi et al., 2016
c.3707-11T>C
Substitution Non-Coding Intron 26 Holstege et al., 2017
c.3707-1G>A
Substitution Non-Coding Intron 26

Unknown.

Unknown.

Campion et al., 2019
R1243C
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Nicolas et al., 2016;
Andersen et al., 2023
R1243P
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
P1245L
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
N1246K
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2, but neutral by Mutation Taster.

Campion et al., 2019
N1246N
(SNP 22)
Substitution Substitution | Silent Coding Exon 27

Unknown, but T allele associated with atrophy of the right middle temporal pole in a sample of non-demented Han Chinese, assessed with MRI.

Predicted tolerated in silico. In a set of autopsy specimens from Caucasian donors with AD, the level of SORL1 protein in the frontal cortex was lower in carriers of the SNP 22 C allele, in a gene-dose-dependent manner.

Rogaeva et al., 2007
C1249S
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
H1255Y
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted to be deleterious by SIFT, PolyPhen-2, and Mutation Taster.

Bellenguez et al., 2017
G1258S
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2017
R1260C
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
D1261G
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
D1267N
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
D1267E
Substitution Substitution | Missense Coding Exon 27

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
Q1269Ter
(Q1269X)
Substitution Substitution | Nonsense Coding Exon 27

Unknown.

Unknown.

Bellenguez et al., 2017
c.3814+10T>G
Substitution Non-Coding Intron 27 Holstege et al., 2017
P1273S
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
C1275S
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
T1276M
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious in silico.

Verheijen et al., 2016
T1276T
Substitution Substitution | Silent Coding Exon 28

Unknown.

Unknown.

Holstege et al., 2017
M1279V
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Holstege et al., 2017
M1279I (G>A)
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown.

Holstege et al., 2022
M1279I (G>T)
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown.

R1286C
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
R1286L
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown.

Holstege et al., 2022
F1291L
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Verheijen et al., 2016
M1294T
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious.

Bellenguez et al., 2017;
Andersen et al., 2023
G1298R
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016
Q1301H
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted to be benign by PolyPhen-2.

Vardarajan et al., 2015;
Andersen et al., 2023
C1302R
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown.

Andersen et al., 2023
C1302Afs
Deletion Deletion | Coding Exon 28

Unknown.

Unknown.

Vardarajan et al., 2015
R1303C
Substitution Substitution | Missense Coding Exon 28

The two carriers who came to autopsy met the CERAD criteria for AD and were Braak stages V-VI.

Using a proximity ligation assay, co-localization of SORL1 and APP was similar in mutation carriers and controls, but less than that seen in sporadic AD.

Thonberg et al., 2017
D1304D
Substitution Substitution | Silent Coding Exon 28

Unknown.

Unknown.

Holstege et al., 2017
G1305E
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
D1309N
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
D1309A
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
A1310V
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted to be tolerated by SIFT, neutral by Mutation Taster, and possibly damaging by PolyPhen-2.

Verheijen et al., 2016
A1310E
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown.

A1311G
Substitution Substitution | Missense Coding Exon 28

Unknown.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
c.3946+2T>C
Substitution Non-Coding Intron 28

Unknown.

Unknown; predicted to be deleterious by Mutation Taster.

Campion et al., 2019
c.3946+5G>A
Substitution Non-Coding Intron 28

Unknown.

Unknown.

Holstege et al., 2022
c.3946+5G>C
Substitution Non-Coding Intron 28

Unknown.

Unknown.

Holstege et al., 2022
c.3946+5G>T
Substitution Non-Coding Intron 28

Unknown.

Unknown.

Holstege et al., 2022
c.3947-3_3947-2insG
Insertion Non-Coding Intron 28

Unknown.

Affects splicing, generating aberrant transcripts containing premature stop codons.

Bellenguez et al., 2017
Q1317Ter
Substitution Substitution | Nonsense Coding Exon 29

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
E1320Sfs
Deletion Deletion | Coding Exon 29

Unknown.

Frame shift.

Holstege et al., 2022
H1322N
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Verheijen et al., 2016
K1323E
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
E1327D
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown.

F1328V
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown.

G1329S
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
C1344R
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
D1345N
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted deleterious.

Fernández et al., 2016
D1345D
Substitution Substitution | Nonsense Coding Exon 29

Unknown.

Unknown.

Holstege et al., 2017
G1346R
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown.

M1347L
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
D1348G
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
G1351S
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
N1358S
Substitution Substitution | Missense Coding Exon 29

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Pottier et al., 2012
E1360K
Substitution Substitution | Missense Coding Exon 29/30

Unknown.

Unknown.

Holstege et al., 2022
c.4078+225T>C
Substitution Non-Coding Intron 29 Reitz et al., 2013
c.4079-85G>A
Substitution Non-Coding Intron 29 Lin et al., 2017
c.4079-43C>G
Substitution Non-Coding Intron 29 Holstege et al., 2017
c.4079-39T>TG
Insertion Non-Coding Intron 29 Holstege et al., 2017
c.4079-1G>C
Substitution Non-Coding Intron 29

Unknown.

Predicted splice-acceptor variant.

E1360G
Substitution Substitution | Missense Coding Exon 29/30

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
N1367D
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown.

R1370H
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown.

Y1371C
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019
Q1373R
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown.

Holstege et al., 2022
Q1373H
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted to be deleterious by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2.

Bellenguez et al., 2017
F1374L
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted deleterious in silico.

Vardarajan et al., 2015;
Andersen et al., 2023
N1378S
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
G1379D
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016
N1384Dfs
(N1384Dfs*48)
Deletion Deletion | Coding Exon 30

Unknown.

Results in a frameshift and the introduction of a premature stop codon.

Holstege et al., 2017
R1385G
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown.

Holstege et al., 2022
D1389V
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted deleterious.

Nicolas et al., 2016;
Andersen et al., 2023
R1390G
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted tolerated in silico.

Sassi et al., 2016
N1392K
Substitution Substitution | Missense Coding Exon 30

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2, but neutral by Mutation Taster.

Rovelet-Lecrux et al., 2021
N1392N
Substitution Substitution | Silent Coding Exon 30

Unknown.

Unknown; predicted tolerated in silico.

T Cuenco et al., 2008
c.4213+1G>A
Substitution Non-Coding Intron 30

Unknown.

Unknown.

Schramm et al., 2022
c.4213+66A>G
Substitution Non-Coding Intron 30

Unknown.

Unknown.

Liu et al., 2017
c.4214-143G>A
Substitution Non-Coding Intron 30

Unknown.

Unknown.

Holstege et al., 2022
c.4214-117G>C
Substitution Non-Coding Intron 30

Unknown.

Unknown.

Wen et al., 2013
L1409F
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but benign by PolyPhen-2 and tolerated by SIFT.

Verheijen et al., 2016
S1412L
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
T1418M
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

Holstege et al., 2022
L1420V
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
N1422S
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown. Predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2. Splicing prediction software indicated that this variant might introduce a novel 3’ splice site, leading to a loss of 52 base pairs and a frameshift.

Bellenguez et al., 2017
Y1423H
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

Holstege et al., 2022
Y1424C
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
R1425H
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

C1431Wfs
Deletion Deletion | Coding Exon 31

Unknown.

Unknown; results in a frame shift and the introduction of a premature stop codon.

Kunkle et al., 2017
T1435S
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated by SIFT and benign by PolyPhen-2.

Vardarajan et al., 2015
D1439N
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

G1440R (G>C)
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
G1440R (G>A)
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2017;
Andersen et al., 2023
G1440V
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
Y1441H
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
Y1441C
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted deleterious.

Sassi et al., 2016;
Andersen et al., 2023
R1442G
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

Holstege et al., 2022
R1442Ter
(R1442X)
Substitution Substitution | Nonsense Coding Exon 31

Unknown.

This protein-truncating variant was predicted to be disease-causing by Mutation Taster.

Verheijen et al., 2016
G1447S
Substitution Substitution | Missense Coding Exon 31

Carrier had autopsy-confirmed AD (amyloid plaques, neurofibrillary tangles, gliosis, and neuron loss), as well as diffuse amyloid angiopathy and Lewy bodies and Lewy neurites in the amygdala.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
A1452G
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

C1453S
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
C1453F
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
P1454S
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2.

Verheijen et al., 2016
L1455W
Substitution Substitution | Missense Coding Exon 31

Unknown.

Unknown.

Holstege et al., 2022
c.4369+5G>A
Substitution Non-Coding Intron 31

Unknown.

Unknown.

Holstege et al., 2022
c.4369+13C>T
Substitution Non-Coding Intron 31 Holstege et al., 2017
c.4369+2223G>A
Substitution Non-Coding Intron 31 Webster et al., 2008
c.4370-1386A>G
Substitution Non-Coding Intron 31 Webster et al., 2008
V1459I
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be tolerated in silico.

Sassi et al., 2016
S1463F
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

T1464P
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

T1464A
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

Q1467H
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be tolerated in silico.

Sassi et al., 2016
R1470Ter
Substitution Substitution | Nonsense Coding Exon 32

Unknown, but amyloid-PET positive. Cortical and hippocampal atrophy and cerebral small vessel disease shown by MRI.

Unknown; predicted to be protein truncating.

Alvarez-Mora et al., 2022
R1470Q
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
R1470L
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Verheijen et al., 2016
D1472G
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

E1477K
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
C1478S
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted deleterious.

Rovelet-Lecrux et al., 2021;
Andersen et al., 2023
C1478Ter
(C1478X)
Substitution Substitution | Nonsense Coding Exon 32

Unknown.

Difference in expression between the wild-type and mutant alleles in blood cells from the carrier of the variant, consistent with nonsense-mediated mRNA decay of the mutant transcript.

Pottier et al., 2012
P1481A
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

P1481R
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
P1481L
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Verheijen et al., 2016
T1483A
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be benign by PolyPhen-2.

Fernández et al., 2016
T1483M
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2, but neutral by Mutation Taster.

Verheijen et al., 2016
R1490C
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
R1490H
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and benign by PolyPhen-2.

Sassi et al., 2016
R1490L
Coding

Unknown.

Unknown.

Holstege et al., 2022
G1493S
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted deleterious.

Sassi et al., 2016;
Andersen et al., 2023
G1493D
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
H1494R
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
C1497Y
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
R1501W
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2, but neutral by Mutation Taster.

Holstege et al., 2017
D1502G
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022
A1504D
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
N1505S
Substitution Substitution | Missense Coding Exon 32

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
P1507S
Substitution Substitution | Missense Coding Exon 32/33

Unknown.

Unknown.

Holstege et al., 2022
c.4519+1G>A
Substitution Non-Coding Intron 32 Bellenguez et al., 2017
c.4519+5G>A
Substitution Non-Coding Intron 32

Carrier had amyloid plaques, neurofibrillary tangles, cerebral amyloid angiopathy, TDP-43 cytoplasmic inclusions in neurons.

Unknown; predicted to cause exon skipping.

Alvarez-Mora et al., 2022
c.4519+1775C>T
Substitution Non-Coding Intron 32 Reitz et al., 2013
c.4519+2811G>A
Substitution Non-Coding Intron 32 Liu et al., 2017
c.4519+3500C>T
Substitution Non-Coding Intron 32 Liu et al., 2017
c.4519+3954A>G
Substitution Non-Coding Intron 32 Liu et al., 2017
c.4519+4139C>G
Substitution Non-Coding Intron 32 Liu et al., 2017
c.4519+4165C>T
Substitution Non-Coding Intron 32 Liu et al., 2017
c.4520-1909G>A
Substitution Non-Coding Intron 32 Bralten et al., 2011
c.4520-1511T>C
Substitution Non-Coding Intron 32 Webster et al., 2008
c.4520-1304T>C
Substitution Non-Coding Intron 32 Webster et al., 2008
c.4520-877T>C
Substitution Non-Coding Intron 32 Liu et al., 2017
c.4520-663A>G
Substitution Non-Coding Intron 32 Bralten et al., 2011
c.4520-13C>G
Substitution Non-Coding Intron 32 Holstege et al., 2017
T1508S
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Holstege et al., 2022
H1509L
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Holstege et al., 2022
S1510N
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Holstege et al., 2022
T1511Lfs
Deletion Deletion | Coding Exon 33

Unknown.

This two-nucleotide deletion results in a frame shift.

Holstege et al., 2022
T1511I
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Vardarajan et al., 2015
C1521R
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
E1522K
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Verheijen et al., 2016
E1525Gfs
Insertion Insertion | Coding Exon 33

Unknown.

This single-nucleotide insertion introduces a frame shift.

Holstege et al., 2022
A1526S
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Holstege et al., 2017
S1531Rfs
Deletion Deletion | Coding Exon 33

Unknown.

This single-nucleotide deletion results in a frame shift.

Holstege et al., 2022
C1534Ter
Substitution Substitution | Nonsense Coding Exon 33

Unknown.

Unknown.

Raghavan et al., 2018
D1535N
Substitution Substitution | Missense Coding Exon 33

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Rovelet-Lecrux et al., 2021
D1535D
Substitution Substitution | Nonsense Coding Exon 33

Unknown.

Unknown.

Holstege et al., 2017
G1536S
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious.

Vardarajan et al., 2015;
Andersen et al., 2023
G1536D
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious.

Campion et al., 2019;
Andersen et al., 2023
C1540S
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
S1541L
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
S1541Wfs
Deletion Deletion | Coding Exon 33

Unknown.

This single-nucleotide deletion results in a frame shift.

Holstege et al., 2022
E1543D
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

Verheijen et al., 2016
D1545N
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious.

Rovelet-Lecrux et al., 2021;
Andersen et al., 2023
D1545G
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
D1545E
Substitution Substitution | Missense Coding Exon 33

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Bellenguez et al., 2017;
Andersen et al., 2023
A1548T
Substitution Substitution | Missense Coding Exon 33

Carrier had autopsy-confirmed AD (amyloid plaques, neurofibrillary tangles, gliosis, and neuron loss), as well as diffuse amyloid angiopathy.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
S1550G
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown; predicted deleterious in silico.

Bellenguez et al., 2017
D1551V
Substitution Substitution | Missense Coding Exon 33

Unknown.

Unknown.

W1563C
Substitution Substitution | Missense Coding Exon 34

Unknown.

Unknown.

Verheijen et al., 2016;
Andersen et al., 2023
T1564A
Substitution Substitution | Missense Coding Exon 34

Unknown.

Unknown.

Holstege et al., 2022
D1566H
Substitution Substitution | Missense Coding Exon 34

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
T1574S
Substitution Substitution | Missense Coding Exon 34

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
W1575Ter
Substitution Substitution | Nonsense Coding Exon 34

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
K1579Q
Substitution Substitution | Missense Coding Exon 34

Unknown.

Unknown.

Holstege et al., 2022
A1584A
(SNP 23)
Substitution Substitution | Silent Coding Exon 34

Unknown.

Unknown, but no effect on SORL1 transcript levels in prefrontal cortices of AD cases or controls.

Rogaeva et al., 2007
R1593S
Substitution Substitution | Missense Coding Exon 34/35

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
V1594M
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
I1599M
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Holstege et al., 2022
E1604G
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
T1605S
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Holstege et al., 2022
N1611K
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
T1612A
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
V1616L
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
L1617V
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Andersen et al., 2023;
Holstege et al., 2023
P1619Q
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Andersen et al., 2023;
Holstege et al., 2023
D1620V
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Holstege et al., 2017
T1622M
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
Q1628Ter
Substitution Substitution | Nonsense Coding Exon 35

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
Q1628R
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Holstege et al., 2022
K1634M
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Du et al., 2019
N1637T
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

N1639Y
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown.

Holstege et al., 2022
V1642M
Substitution Substitution | Missense Coding Exon 35

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2 , but neutral by Mutation Taster.

Rovelet-Lecrux et al., 2021
L1644Ter
Deletion Deletion | Coding Exon 35

Unknown.

Unknown.

Vardarajan et al., 2015
c.4949-458G>A
Substitution Non-Coding Intron 35

Unknown.

Unknown.

Webster et al., 2008
A1653S
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
P1654S
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted deleterious in silico.

Bellenguez et al., 2017;
Andersen et al., 2023
P1654L
Substitution Substitution | Missense Coding Exon 36

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Nicolas et al., 2016;
Andersen et al., 2023
R1655Ter
(R1655X)
Substitution Substitution | Nonsense Coding Exon 36

Unknown.

This single-nucleotide substitution introduces a premature stop codon.

Bellenguez et al., 2017
R1655Q
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted tolerated in silico.

Rovelet-Lecrux et al., 2021
L1657F
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
L1661F
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown.

Fernández et al., 2016;
Andersen et al., 2023
V1668M
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted to be damaging by SIFT, benign by Mutation Taster, and probably damaging by PolyPhen-2.

Verheijen et al., 2016
I1669T
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
A1674T
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted tolerated in silico.

Rovelet-Lecrux et al., 2021
P1675S
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown.

Holstege et al., 2017
I1677L
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown.

H1678D
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown.

T1679I
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2 , but neutral by Mutation Taster.

Campion et al., 2019
H1680D
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
H1680H
Substitution Substitution | Silent Coding Exon 36

Unknown.

Unknown.

Holstege et al., 2017
G1681D
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted deleterious.

Pottier et al., 2012
R1684H
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown.

Holstege et al., 2022
I1687M
Substitution Substitution | Missense Coding Exon 36

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
c.5061+1G>T
Substitution Non-Coding Intron 36

Unknown.

Predicted splice-donor variant.

c.5062-79C>T
Substitution Non-Coding Intron 36 Wen et al., 2013
c.5062-16T>G
Substitution Non-Coding Intron 36 Holstege et al., 2017
M1697I (G>C)
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown; predicted tolerated in silico.

Holstege et al., 2017
M1697I (G>A)
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown; predicted tolerated in silico.

Verheijen et al., 2016
W1698C
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
Q1701R
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
R1702M
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown; predicted to be damaging by PolyPhen-2.

Gómez-Tortosa et al., 2018
I1710T
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
T1717A
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
V1721I
Substitution Substitution | Missense Coding Exon 37

Unknown.

Unknown.

Andersen et al., 2023
c.5167-318C>T
Substitution Non-Coding Intron 37 Webster et al., 2008
R1729G
Substitution Substitution | Missense Coding Exon 38

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
R1729H
Substitution Substitution | Missense Coding Exon 38

Unknown.

Unknown; predicted to be deleterious by SIFT, disease-causing by Mutation Taster, and probably damaging by PolyPhen-2.

Holstege et al., 2017
I1731M
Substitution Substitution | Missense Coding Exon 38

Unknown.

Unknown.

Holstege et al., 2022
G1732A
Substitution Substitution | Missense Coding Exon 38

Unknown. MRI of two carriers clinically diagnosed with AD showed hippocampal and cortical atrophy, and small hemorrhages in cortical regions.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Thonberg et al., 2017
c.5239+1G>A
Substitution Non-Coding Intron 38

Unknown.

Unknown.

Holstege et al., 2022
c.5239+73C>T
(SNP 24)
Substitution Non-Coding Intron 38

Does not affect SORL1 protein levels in brains of AD cases or SORL1 expression in response to BDNF of IPSC-derived neurons.

Rogaeva et al., 2007
c.5240-378C>T
Substitution Non-Coding Intron 38 Seshadri et al., 2007
I1748Sfs
Deletion Deletion | Coding Exon 38-39

Unknown.

This single-nucleotide deletion results in a frameshift.

Verheijen et al., 2016
P1751T
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
I1753V
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
H1754N
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
I1755T
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown.

Andersen et al., 2023
I1755M
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
Y1758C
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown.

Holstege et al., 2022
F1765C
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
F1765F
Substitution Substitution | Silent Coding Exon 39

Unknown.

Unknown; predicted to be tolerated by SIFT, disease-causing by Mutation Taster, and neutral by PROVEAN.

El Bitar et al., 2019
T1768A
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
T1768I
Substitution Substitution | Missense Coding Exon 39

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
c.5323-507C>A
Substitution Non-Coding Intron 39 Webster et al., 2008
c.5323-44C>T
(SNP 25)
Substitution Non-Coding Intron 39

Does not affect SORL1 protein levels in brains of AD cases or SORL1 expression in response to BDNF of IPSC-derived neurons.

Rogaeva et al., 2007
V1775L
Substitution Substitution | Missense Coding Exon 40

Unknown.

Unknown.

Holstege et al., 2022
L1796L
Substitution Substitution | Silent Coding Exon 40

Unknown.

Unknown.

Nicolas et al., 2018
R1799Ter
(R1799X)
Substitution Substitution | Nonsense Coding Exon 40

Unknown.

Introduces a premature stop codon.

Schramm et al., 2022
R1799Q
Substitution Substitution | Missense Coding Exon 40

Unknown.

Unknown; predicted tolerated in silico.

Geut et al., 2019
H1805P
Substitution Substitution | Missense Coding Exon 40

Unknown.

Unknown.

c.5419+1G>A
Substitution Non-Coding Intron 40

Unknown.

Unknown.

Holstege et al., 2022
c.5419+6A>G
Substitution Non-Coding Intron 40 Holstege et al., 2017
c.5419+110G>A
Substitution Non-Coding Intron 40 Bralten et al., 2011
N1809S
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Verheijen et al., 2016;
Gómez-Tortosa et al., 2018
H1813R
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted to tolerated by SIFT and benign by PolyPhen-2, but deleterious by Mutation Taster.

Verheijen et al., 2016
H1813Q
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted to be be benign by PolyPhen-2, tolerated by SIFT, and deleterious by Mutation Taster.

Verheijen et al., 2016
T1814I
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Y1816C
Substitution Substitution | Missense Coding Exon 41

Unknown.

Impairs SORL1 maturation (glycosylation), dimerization, co-localization with retromer, and trafficking to the plasma membrane, resulting in endosomal swelling and decreased levels of soluble SORL1.

Verheijen et al., 2016;
Jensen et al., 2023
Y1816Y
Substitution Substitution | Silent Coding Exon 41

Unknown.

Unknown.

Holstege et al., 2017
W1821Ter
(W1821X)
Substitution Substitution | Nonsense Coding Exon 41

Unknown.

Unknown; predicted to be disease-causing by Mutation Taster.

Pottier et al., 2012
T1824A
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted to be deleterious by SIFT, but neutral/benign by Mutation Taster and PolyPhen-2.

Campion et al., 2019
D1828Ifs
Deletion Deletion | Coding Exon 41

Unknown.

This single-nucleotide deletion results in a frame shift.

Holstege et al., 2022
D1828V
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
P1830S
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Holstege et al., 2022
H1835Q
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Holstege et al., 2022
P1844S
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
P1846H
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
A1850T
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
A1852T
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Holstege et al., 2022
I1853V
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
V1858A
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown.

Andersen et al., 2023
C1860Yfs
Deletion Deletion | Coding Exon 41

Unknown.

This two-nucleotide deletion results in a frame shift.

Holstege et al., 2022
C1860Ter
Substitution Substitution | Nonsense Coding Exon 41

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
W1862C
Substitution Substitution | Missense Coding Exon 41

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Rovelet-Lecrux et al., 2021
R1866W
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted to be deleterious by SIFT and PolyPhen-2, but neutral by Mutation Taster.

Holstege et al., 2017
R1866Q
Substitution Substitution | Missense Coding Exon 41

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
c.5604+788C>A
Substitution Non-Coding Intron 41 Driscoll et al., 2019
c.5604+1843A>G
Substitution Non-Coding Intron 41 Liu et al., 2017
c.5605-67G>A
(SNP 26)
Substitution Non-Coding Intron 41 Rogaeva et al., 2007
c.5605-3C>T
Substitution Non-Coding Intron 41 Nicolas et al., 2018
G1871V
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown.

Gómez-Tortosa et al., 2018
F1873Y
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Fernández et al., 2016
T1876M
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
R1883C
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown.

P1885S
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Verheijen et al., 2016
P1885L
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
K1886R
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown.

T1889I
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown.

L1892H
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
K1895K
Substitution Substitution | Silent Coding Exon 42

Unknown.

Unknown; predicted to be tolerated by SIFT and neutral by PROVEAN, and it was classified as a polymorphism by Mutation Taster.

Verheijen et al., 2016
T1896M
Substitution Substitution | Missense Coding Exon 42

Unknown.

Unknown.

c.5724+2T>C
Substitution Non-Coding Intron 42

Unknown.

Predicted splice-donor variant.

c.5724+16C>T
Substitution Non-Coding Intron 42 Holstege et al., 2017
c.5724+203G>A
Substitution Non-Coding Intron 42 Liu et al., 2017
V1909I
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Holstege et al., 2022;
Andersen et al., 2023
R1910H
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Verheijen et al., 2016;
Andersen et al., 2023
P1914S
Substitution Substitution | Missense Coding Exon 43

Unknown.

Impaired maturation (glycosylation) and trafficking to the plasma membrane of SORL1 overexpressed in HEK293 cells.

Bellenguez et al., 2017
Y1915C
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
Y1922S
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown; predicted to be tolerated by SIFT and benign by PolyPhen-2, but deleterious by Mutation Taster.

Fernández et al., 2016
K1926N
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

R1936H
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
H1942R
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Holstege et al., 2022
T1943P
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Holstege et al., 2022
T1943K
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Holstege et al., 2022
T1943R
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Holstege et al., 2022
T1943M
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown.

Holstege et al., 2022
G1944Efs
Deletion Deletion | Coding Exon 43

Unknown.

This two-nucleotide deletion results in a frameshift and is predicted to be protein-truncating.

Bellenguez et al., 2017
K1945N
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
P1955L
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown; predicted deleterious.

Verheijen et al., 2016;
Andersen et al., 2023
S1958C
Substitution Substitution | Missense Coding Exon 43

Unknown.

Unknown; predicted to be damaging by SIFT, disease-causing by Mutation Taster, and possibly damaging by PolyPhen-2.

Verheijen et al., 2016
c.5890-515C>T
Substitution Non-Coding Intron 43 Liu et al., 2017
c.5890-15C>CT
Insertion Non-Coding Intron 43 Holstege et al., 2017
V1967I
(I1967V)
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted tolerated.

Vardarajan et al., 2015;
Andersen et al., 2023
D1971Y
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

Holstege et al., 2022
K1975Lfs
Deletion Deletion | Coding Exon 44

Unknown.

This five-nucleotide deletion results in a frame shift and introduces a premature stop codon.

Campion et al., 2019
S1979N
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted to be benign by PolyPhen-2.

Fernández et al., 2016
S1979Ifs
Deletion Deletion | Coding Exon 44

Unknown.

This two-nucleotide deletion results in a frame shift.

Holstege et al., 2022
R1985C
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Rovelet-Lecrux et al., 2021
N1986Ter
Insertion Insertion | Nonsense Coding Exon 44

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
V1989A
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

L1993F
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019;
Andersen et al., 2023
E1997D
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
G2000R
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Holstege et al., 2017
I2004L
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

Campion et al., 2019;
Andersen et al., 2023
Q2007Q
Substitution Substitution | Nonsense Coding Exon 44

Unknown.

Unknown.

Holstege et al., 2017
G2009E
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

M2011V
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

S2012T
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

D2014N
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Verheijen et al., 2016
S2016G
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

I2017R
Substitution Substitution | Missense Coding Exon 44

Unknown.

Unknown.

V2022A
Substitution Substitution | Missense Coding Exon 44/45

Unknown.

Unknown.

S2023L
Substitution Substitution | Missense Coding Exon 45

Unknown.

Unknown.

A2029T
Substitution Substitution | Missense Coding Exon 45

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
I2033V
Substitution Substitution | Missense Coding Exon 45

Unknown.

Unknown.

Holstege et al., 2022
H2038D
Substitution Substitution | Missense Coding Exon 45

Unknown, but one carrier reported to be amyloid-PET positive.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Verheijen et al., 2016
K2044R
Substitution Substitution | Missense Coding Exon 45

Unknown.

Unknown.

Csaban et al., 2022
E2055Ter
(E2055X)
Substitution Substitution | Nonsense Coding Exon 45

Unknown.

This single-nucleotide substitution introduces a premature stop codon.

Nicolas et al., 2016
c.6171+24T>G
(SNP 27)
Substitution Non-Coding Intron 45 Rogaeva et al., 2007
c.6171+1050C>T
Substitution Non-Coding Intron 45 Webster et al., 2008
c.6171+1112C>T
Substitution Non-Coding Intron 45 Webster et al., 2008
c.6172-239G>A
Substitution Non-Coding Intron 45 Bralten et al., 2011
c.6172-3C>T
Substitution Non-Coding Intron 45 Holstege et al., 2017
Y2059C
Substitution Substitution | Missense Coding Exon 46

Unknown.

Predicted deleterious.

Holstege et al., 2022;
Andersen et al., 2023
D2065V
Substitution Substitution | Missense Coding Exon 46

Unknown.

Predicted damaging in silico.

Vardarajan et al., 2015
D2065E
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
M2068V
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
M2068I
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

T2071A
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

Holstege et al., 2022
A2072V
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be deleterious by SIFT and Mutation Taster, but benign by PolyPhen-2.

Campion et al., 2019
Y2073Ter
Substitution Substitution | Nonsense Coding Exon 46

Unknown.

Introduces a premature stop codon.

Holstege et al., 2022
G2075A
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Rovelet-Lecrux et al., 2021
T2078I
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

Holstege et al., 2022
D2079N
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Holstege et al., 2017
K2083R
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be tolerated by SIFT and benign by PolyPhen-2, but deleterious by Mutation Taster.

Vardarajan et al., 2015
N2086I
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

Holstege et al., 2022
N2086T
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

Holstege et al., 2022
G2090C
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
G2090V
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Verheijen et al., 2016
H2091R
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

Y2093Ter
Substitution Substitution | Nonsense Coding Exon 46

Unknown.

Introduces a premature stop codon.

Schramm et al., 2022
T2094M
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

T2096I
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

V2097I
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown.

Verheijen et al., 2016
A2099G
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted deleterious.

Fernández et al., 2016;
Andersen et al., 2023
Q2106Q
Substitution Substitution | Nonsense Coding Exon 46

Unknown.

Unknown; predicted to be tolerated by SIFT, neutral by PROVEAN, and disease-causing by Mutation Taster.

Holstege et al., 2017
D2117N
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be deleterious by Mutation Taster, but tolerated/benign by SIFT and PolyPhen-2.

Campion et al., 2019
L2119P
Substitution Substitution | Missense Coding Exon 46

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
c.6365-380T>C
Substitution Non-Coding Intron 46 Webster et al., 2008
Q2129R
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted tolerated in silico.

Campion et al., 2019
A2131T
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted tolerated in silico.

El Bitar et al., 2019
T2134M
Substitution Substitution | Missense Coding Exon 47

Unknown.

Appears to reduce trafficking of SORL1 to the cell surface and to disrupt its binding to APP.

Cuccaro et al., 2016
F2145L
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

I2147M
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted to be damaging by SIFT, but benign by Mutation Taster and PolyPhen-2.

Verheijen et al., 2016
I2157V
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2022
L2158L
Substitution Substitution | Nonsense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2017
T2160M
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted to be tolerated by SIFT and benign by PolyPhen-2, but deleterious by Mutation Taster.

Holstege et al., 2017
T2160R
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2022
R2163W
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2022
R2164Gfs
Deletion Deletion | Coding Exon 47

Unknown.

This single-nucleotide deletion results in a frameshift leading to a premature stop codon.

Vardarajan et al., 2015
R2163Q
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted to be probably damaging by PolyPhen-2.

Fernández et al., 2016
A2171T
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
A2173T
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Gómez-Tortosa et al., 2018
N2174S
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted deleterious in silico.

Verheijen et al., 2016
S2175R (C>G)
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Sassi et al., 2016
S2175R (C>A)
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
H2176R
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown; predicted to be deleterious by SIFT, Mutation Taster, and PolyPhen-2.

Bellenguez et al., 2017
L2181P
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2022
A2184T
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2022
I2185V
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

D2190N
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

Holstege et al., 2022
D2191N
Substitution Substitution | Missense Coding Exon 47

Unknown.

Unknown.

E2194K
Substitution Substitution | Missense Coding Exon 48

Unknown.

Unknown; predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2.

Campion et al., 2019
D2207G
Substitution Substitution | Missense Coding Exon 48

Unknown.

Unknown; predicted deleterious in silico.

Campion et al., 2019
M2211Hfs
Insertion Insertion | Coding Exon 48

Unknown.

This single-nucleotide insertion introduces a frame shift.

Holstege et al., 2022
c.*267T>C
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*966G>A
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*1020A>G
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*1134T>C
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*1483G>A
(SNP 28)
Substitution Non-Coding 3′UTR Rogaeva et al., 2007
c.*2473C>G
(SNP 29)
Substitution Non-Coding 3′UTR Rogaeva et al., 2007
c.*2496A>G
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*2622T>C
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*3216C>G
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*3556A>G
Substitution Non-Coding 3' UTR Zhang et al., 2015
c.*3909A>C
Substitution Non-Coding 3' UTR Zhang et al., 2015