Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227071565 G>A
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GTG to ATG
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 5


This variant was detected in an individual with apparently sporadic AD (Frigerio et al., 2015). There was no family history of dementia. Other than the diagnosis, clinical details related to this individual were not reported. 

Three heterozygote carriers of this variant, two of European ancestry and one of African ancestry, were reported in the gnomAD variant database (v2.1.1, Nov 2021). The global frequency was 0.00001194.



Biological Effect

The biological effect of this variant is unknown, but the residue is conserved between PSEN1 and PSEN2 (Hsu et al., 2020). Moreover, in silico, this variant was predicted to be probably damaging by PolyPhen-2, and its PHRED-scaled CADD score, which integrates diverse information in silico, was above 20, suggesting a deleterious effect (CADD v.1.6, Nov 2021) .


Last Updated: 01 Dec 2021


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Paper Citations

  1. . Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiol Dis. 2020 Jun;139:104817. Epub 2020 Feb 19 PubMed.

Other Citations

  1. Frigerio et al., 2015

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . On the identification of low allele frequency mosaic mutations in the brains of Alzheimer's disease patients. Alzheimers Dement. 2015 Apr 29; PubMed.


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