APBB2 p.Ala279Val
c.836C>T · rs199964463 · VCV2343413
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.157%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.082 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor loss, 3 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.79 | unconstrained · MANE · 217 kb · p 1.3e-10 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.157%
Middle Eastern · 7/4,470 alleles
Filtering AF
0.0735%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.052%
Overall
0.0342%
402/1,175,900 alleles · rare
exomes 373/1,039,588 · genomes 29/136,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.157% | 639 |
| Remaining individualsnot grpmax-eligible | 0.0622% | 1,608 |
| European (non-Finnish) | 0.04% | 2,500 |
| Admixed American | 0.0259% | 3,858 |
| African / African-American | 0.0114% | 8,744 |
| South Asian | 0.0111% | 9,020 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00477% | 20,980 |
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
- APBB2
- Protein
- p.Ala279Val
- Coding
- c.836C>T
- MANE Select
- NM_004307
- dbSNP
- rs199964463
- Type
- single nucleotide variant
- Location
- chr4:40945073 (GRCh38)
- Gene constraint
- LOEUF 0.54 · pLI 0.61 (gnomAD)
- Structure
- AlphaFold pLDDT 61.73
- Residue 279
- the 'disordered' region
Similar variants
- APBB2 c.20-6C>T Benign ★★ same type
- APBB2 p.Ala111Val Uncertain significance ★ ⚠ same type
- APBB2 p.Ala126Val Uncertain significance ★ ⚠ same type
- APBB2 p.Ala197Val Uncertain significance ★ ⚠ same type
- APBB2 p.Ala224Asp Uncertain significance ★ ⚠ same type
- APBB2 p.Ala436Pro Uncertain significance ★ ⚠ same type
- APBB2 p.Ala436Thr Uncertain significance ★ ⚠ same type
- APBB2 p.Ala558Val Uncertain significance ★ ⚠ same type
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/apbb2-p-ala279val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown