Pathogenicity: Alzheimer's Disease : Not Pathogenic
Clinical Phenotype: Alzheimer's Disease, None
Reference Assembly: GRCh37 (105)
Position: Chr14:73637521 G>A
dbSNP ID: rs63750592
Coding/Non-Coding: Coding
Genomic Region: Exon 4
Mutation Type: Point, Missense
Codon Change: CGG to CAG


Although this coding variant has been identified in at least two individuals with Alzheimer's disease, it has not been associated with familial disease. Given the lack of evidence for segregation with disease and the fact that the affected residue is not conserved in presenilin-2, this variant is thought to be a rare benign polymorphism.

This variant was detected in one out of 414 Alzheimer's disease patients who were thought to carry genetic risk factors. Segregation analysis was not possible (Rogaeva et al., 2001).

The variant was later found in one Mozabite individual among 130 DNA samples obtained from the Centre d'Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP) (Guerreiro et al., 2010).

Whole-exome sequencing also identified this variant in one of 424 French people with early onset AD. Clinical details were not reported (Nicolas et al., 2015).


Not applicable.

Biological Effect

Unknown. This variant is predicted benign by in silico analysis.


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Paper Citations

  1. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.
  2. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.
  3. . Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. Eur J Hum Genet. 2015 Aug 5; PubMed.

Further Reading


  1. . Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update. J Med Genet. 2005 Oct;42(10):793-5. Epub 2005 Jul 20 PubMed.

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

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Primary Papers

  1. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.