AFF3 p.Ala396=
c.1188C>T · rs4851214 · VCV1243294
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 36.7%, eas) — 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 | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.59 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -1.3 |
| Overall | ||
| CADD | 9.816 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
36.7%
East Asian · 16,309/44,492 alleles
Filtering AF
36.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 36%
Overall
27.3%
434,943/1,590,294 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 36.7% | 3 |
| South Asian | 34.6% | 3 |
| Middle Eastern | 29.6% | 3 |
| Amishnot grpmax-eligible | 29.5% | 3 |
| European (non-Finnish) | 28.3% | 4 |
| Remaining individualsnot grpmax-eligible | 27.3% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 24.8% | 4 |
| Finnishnot grpmax-eligible | 23% | 4 |
| Admixed American | 22.9% | 4 |
| African / African-American | 4.98% | 20 |
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.Ala396=
- Coding
- c.1188C>T
- MANE Select
- NM_001386135
- dbSNP
- rs4851214
- Type
- single nucleotide variant
- Location
- chr2:99601618 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.20
- Residue 396
- the 'disordered' region
Similar variants
- AFF3 p.Ala396Thr Likely benign ★ same residue
- 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
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-ala396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown