APP p.Val711=
c.2133C>A · rs116650065 · VCV339628
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.82%, afr)
Conditions
1
Alzheimer disease
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 9.091 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.82%
African / African-American · 2,117/75,018 alleles
Filtering AF
2.72%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.68%
Overall
0.15%
2,417/1,614,042 alleles · low-frequency
exomes 1,198/1,461,806 · genomes 1,219/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.82% | 35 |
| Remaining individualsnot grpmax-eligible | 0.211% | 474 |
| Admixed American | 0.153% | 652 |
| Middle Eastern | 0.116% | 865 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0777% | 1,287 |
| South Asian | 0.00439% | 22,767 |
| European (non-Finnish) | 0.00356% | 28,095 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- APP
- Protein
- p.Val711=
- Coding
- c.2133C>A
- MANE Select
- NM_000484
- dbSNP
- rs116650065
- Type
- single nucleotide variant
- Location
- chr21:25891800 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.11 · 263 PDB
- Residue 711
- a β-strand; the 'interaction with psen1' region; a functional site (cleavage; by gamma-secretase; site 1)
Similar variants
- APP p.Ala713Thr Likely pathogenic ★★ ⚠ same condition
- APP p.Asp694Asn Pathogenic ★★ ⚠ same condition
- APP p.Glu693Gln Pathogenic ★★ ⚠ same condition
- APP p.Ile716Phe Pathogenic ★★ ⚠ same condition
- APP p.Thr714Ala Pathogenic ★★ ⚠ same condition
- APP p.Val715Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
- APP p.Val717Ile Pathogenic ★★ ⚠ same condition
- APP p.Val717Phe Pathogenic ★★ ⚠ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/app-p-val711 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown