AFF4 p.Ser886Thr
c.2656T>A · rs779261547 · VCV2502245
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0618 | likely benign |
|---|---|---|
| REVEL | 0.023 | moderately benign-leaning |
| SaProt | LLR -8.03 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8 | GERP 3, phastCons 1 |
| Regional constraint | o/e 1.05 | unconstrained · MANE · 7,535 bp · p 0.44 · regional, not allelic |
| Overall | ||
| CADD | 19.94 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0681% | 1,468 |
| Middle Eastern | 0.0493% | 2,027 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,822 |
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
- AFF4
- Protein
- p.Ser886Thr
- Coding
- c.2656T>A
- MANE Select
- NM_014423
- dbSNP
- rs779261547
- Type
- single nucleotide variant
- Location
- chr5:132889155 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.62 · 9 PDB
- Residue 886
- the 'disordered' region
Similar variants
- AFF4 p.Arg258Trp Pathogenic/Likely pathogenic ★★ same condition
- AFF4 p.Met260Val Likely pathogenic ★★ ⚠ same condition
- AFF4 p.Pro253Leu Pathogenic/Likely pathogenic ★★ same condition
- AFF4 p.Thr254Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AFF4 c.1133+3A>G Uncertain significance ★★ same condition
- AFF4 p.Ala114Thr Uncertain significance ★★ ⚠ same condition
- AFF4 p.Ala114Val Uncertain significance ★★ ⚠ same condition
- AFF4 p.Ala27Thr Uncertain significance ★★ ⚠ same condition
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/aff4-p-ser886thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown