Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.76%, afr)
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 -0.15 | GERP -4.7, phastCons 0.006 |
| Overall | ||
| CADD | 6.605 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.76%
African / African-American · 3,566/74,934 alleles
Filtering AF
4.63%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.58%
Overall
0.264%
4,258/1,613,886 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.76% | 21 |
| Middle Eastern | 0.446% | 224 |
| Remaining individualsnot grpmax-eligible | 0.389% | 257 |
| Admixed American | 0.374% | 268 |
| European (non-Finnish) | 0.0157% | 6,378 |
| South Asian | 0.0121% | 8,280 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,799 |
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
- AFF1
- Protein
- p.Ala40=
- Coding
- c.120A>G
- MANE Select
- NM_001166693
- dbSNP
- rs7689167
- Type
- single nucleotide variant
- Location
- chr4:87046247 (GRCh38)
- Gene constraint
- LOEUF 0.49 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 53.06 · 1 PDB
- Residue 40
- the 'disordered' region
Similar variants
- AFF1 c.1191+8C>T Benign/Likely benign ★★ same type
- AFF1 p.Pro393= Benign ★★ same type
- AFF1 p.Ser627Cys Likely benign ★★ same type
- AFF1 p.Thr426= Likely benign ★★ same type
- AFF1 p.Val711Ile Benign ★★ same type
- AFF1 p.Ala1047Val Uncertain significance ★ ⚠ same type
- AFF1 p.Ala1103Thr Uncertain significance ★ ⚠ same type
- AFF1 p.Ala127Val 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/aff1-p-ala40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown