AFF3 p.Ala596=
c.1788C>T · rs1558618600 · VCV1694962
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00851%, 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 -7.7 | GERP -4.7 |
| Overall | ||
| CADD | 6.121 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00851%
African / African-American · 6/70,476 alleles
Filtering AF
0.00365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0025%
Overall
0.000645%
9/1,394,404 alleles · very rare
exomes 8/1,255,530 · genomes 1/138,874 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00851% | 11,746 |
| Admixed American | 0.00221% | 45,158 |
| Remaining individualsnot grpmax-eligible | 0.0019% | 52,748 |
| European (non-Finnish) | 9.65e-05% | 1,036,255 |
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.Ala596=
- Coding
- c.1788C>T
- MANE Select
- NM_001386135
- dbSNP
- rs1558618600
- Type
- single nucleotide variant
- Location
- chr2:99593873 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.20
- Residue 596
- the 'disordered' region
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-ala596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown