AFF3 p.Ala279=
c.837C>T · rs34506074 · VCV1270586
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 7.96%, afr) — too common for a highly-penetrant pathogenic allele
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 5.2 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 11.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.96%
African / African-American · 5,968/74,994 alleles
Filtering AF
7.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.72%
Overall
1.47%
23,623/1,611,978 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.96% | 13 |
| Middle Eastern | 5.55% | 18 |
| Ashkenazi Jewishnot grpmax-eligible | 4.85% | 21 |
| South Asian | 2.12% | 47 |
| Remaining individualsnot grpmax-eligible | 1.94% | 52 |
| Admixed American | 1.19% | 84 |
| European (non-Finnish) | 0.993% | 101 |
| Finnishnot grpmax-eligible | 0.511% | 196 |
| East Asian | 0.00892% | 11,204 |
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
- AFF3
- Protein
- p.Ala279=
- Coding
- c.837C>T
- MANE Select
- NM_001386135
- dbSNP
- rs34506074
- Type
- single nucleotide variant
- Location
- chr2:100006668 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.20
- Residue 279
- the 'disordered' region
Similar variants
- AFF3 p.Ala233Thr Pathogenic ★★ ⚠ same type
- AFF3 p.Ala233Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- AFF3 p.Ile1147Asn Uncertain significance ★★ ⚠ same type
- AFF3 p.Leu370Phe Uncertain significance ★★ ⚠ same type
- AFF3 p.Pro321Leu Uncertain significance ★★ ⚠ same type
- AFF3 p.Ser222Thr Uncertain significance ★★ ⚠ same type
- AFF3 p.Thr950Met Uncertain significance ★★ ⚠ same type
- AFF3 c.1371+7G>A Likely benign ★★ 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/aff3-p-ala279 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown