rs63750847

goodMag 6.5

This is a variant in the APP gene that changes a alanine to an threonine.

Key Literature Trait Associations

Alzheimer's Disease (Protective)

The A673T substitution in amyloid precursor protein (APP) is a rare protective variant discovered in the Icelandic population by deCODE Genetics. Carriers produce approximately 40% less amyloidogenic amyloid-beta peptides in vitro, as the mutation lies adjacent to the beta-secretase (BACE1) cleavage site and reduces enzymatic processing. The variant confers strong protection against Alzheimer's disease (OR ≈ 0.24) and is also associated with slower cognitive decline in elderly non-demented carriers, in a study of ~1,795 AD patients vs. 401,638 controls.

Jonsson T et al. “A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.” Nature 488(7409):96-99 (2012)

Allele C

OR 0.24

p 1.1e-10

Large GWAS

Wang LS et al. “Rarity of the Alzheimer disease-protective APP A673T variant in the United States.” Jama Neurology (2015)

Allele C

OR —

p —

N 20,986

Preliminary work

European American

Bamne MN et al. “Investigation of an amyloid precursor protein protective mutation (A673T) in a North American case-control sample of late-onset Alzheimer's disease.” Neurobiology of Aging (2014)

Allele C

OR —

p —

N 4,318

Preliminary work

North American White

Wittrahm R et al. “Protective Alzheimer's disease-associated APP A673T variant predominantly decreases sAPPβ levels in cerebrospinal fluid and 2D/3D cell culture models.” Neurobiology of Disease (2023)

Allele C

OR —

p —

N 6

Candidate gene study

Northern European

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ClinVar annotation

Benign★☆☆☆

3 submitters2 publications

Alzheimer disease; Alzheimer disease, protection against

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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