AFF1 p.Thr426=
c.1278G>A · rs145877283 · VCV749296
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.462%, 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 -0.64 | GERP -0.64, phastCons 0.99 |
| Overall | ||
| CADD | 7.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.462%
Middle Eastern · 28/6,060 alleles
Filtering AF
0.328%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.283%
Overall
0.0121%
195/1,612,940 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.462% | 216 |
| African / African-American | 0.0493% | 2,027 |
| South Asian | 0.0373% | 2,678 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,941 |
| European (non-Finnish) | 0.00721% | 13,870 |
| East Asian | 0.00223% | 44,874 |
| Admixed American | 0.00167% | 60,012 |
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.Thr426=
- Coding
- c.1278G>A
- MANE Select
- NM_001166693
- dbSNP
- rs145877283
- Type
- single nucleotide variant
- Location
- chr4:87094964 (GRCh38)
- Gene constraint
- LOEUF 0.49 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 53.06 · 1 PDB
- Residue 426
- the 'disordered' region
Similar variants
- AFF1 c.1191+8C>T Benign/Likely benign ★★ same type
- AFF1 p.Ala40= Benign ★★ same type
- AFF1 p.Pro393= Benign ★★ same type
- AFF1 p.Ser627Cys 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-thr426 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown