Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73664813 C>T
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTT to TTT
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 8


This mutation was identified in a Japanese woman diagnosed with probable Alzheimer’s disease based on NINCDS-ADRDA criteria (Hamaguchi et al., 2009). She started to develop memory impairment at age 53. She had a family history of dementia, but genetic analysis was performed only on the proband. Her sister was diagnosed with dementia at the age of 49. The proband's mother died at the age of 80 without dementia. Two of the mother’s five siblings developed dementia, one in her 60s and one in her 50s. The proband’s father had died young without dementia. Information is not available about the paternal line, therefore it remains unclear if the mutation was transmitted through the maternal line with incomplete penetrance observed in the proband’s mother.

This variant was absent from the gnomAD variant database (gnomAD v2.1.1, July 2021).


Unknown. MRI of the proband showed mild medial temporal atrophy. FDG-PET showed glucose hypometabolism in the bilateral parietal cortices and posterior cingulate gyri (Hamaguchi et al., 2009).

Biological Effect

The biological effect of this variant is unknown, but several in silico algorithms (SIFT, Polyphen-2, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, CADD, REVEL, and Reve in the VarCards database) predicted this variant is damaging (Xiao et al., 2021).

Last Updated: 13 Sep 2021


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Paper Citations

  1. . A novel presenilin 1 mutation (L282F) in familial Alzheimer's disease. J Neurol. 2009 Sep;256(9):1575-7. PubMed.
  2. . APP, PSEN1, and PSEN2 Variants in Alzheimer's Disease: Systematic Re-evaluation According to ACMG Guidelines. Front Aging Neurosci. 2021;13:695808. Epub 2021 Jun 18 PubMed.

External Citations

  1. gnomAD v2.1.1

Further Reading


  1. . Derivation of induced pluripotent stem cells from a familial Alzheimer's disease patient carrying the L282F mutation in presenilin 1. Stem Cell Res. 2016 Sep 28;17(3):470-473. PubMed.

Protein Diagram

Primary Papers

  1. . A novel presenilin 1 mutation (L282F) in familial Alzheimer's disease. J Neurol. 2009 Sep;256(9):1575-7. PubMed.

Other mutations at this position


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