AFF3 p.Ala1158=
c.3474G>A · rs141110020 · VCV2651182
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.181%, mid)
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 -6.8 | GERP -3.8 |
| Overall | ||
| CADD | 8.433 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.181%
Middle Eastern · 11/6,062 alleles
Filtering AF
0.129%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.121%
Overall
0.107%
1,726/1,614,150 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.181% | 551 |
| South Asian | 0.149% | 670 |
| European (non-Finnish) | 0.118% | 846 |
| Remaining individualsnot grpmax-eligible | 0.107% | 933 |
| Admixed American | 0.0783% | 1,277 |
| Finnishnot grpmax-eligible | 0.0609% | 1,642 |
| African / African-American | 0.0307% | 3,262 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0236% | 4,229 |
| East Asian | 0.00223% | 44,884 |
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.Ala1158=
- Coding
- c.3474G>A
- MANE Select
- NM_001386135
- dbSNP
- rs141110020
- Type
- single nucleotide variant
- Location
- chr2:99554396 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.20
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-ala1158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown