AFF2 p.Ala596=
c.1788C>A · rs149492076 · VCV767150
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.243%, nfe)
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 -0.4 | GERP 1, phastCons 0.03 |
| Overall | ||
| CADD | 5.298 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.243%
European (non-Finnish) · 2,178/895,145 alleles
Filtering AF
0.235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.231%
Overall
0.188%
2,273/1,209,561 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.243% | 411 |
| Remaining individualsnot grpmax-eligible | 0.113% | 882 |
| African / African-American | 0.0316% | 3,167 |
| Middle Eastern | 0.023% | 4,349 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0182% | 5,506 |
| Admixed American | 0.0153% | 6,531 |
| South Asian | 0.0123% | 8,103 |
| Finnishnot grpmax-eligible | 0.00859% | 11,638 |
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
- AFF2
- Protein
- p.Ala596=
- Coding
- c.1788C>A
- MANE Select
- NM_002025
- dbSNP
- rs149492076
- Type
- single nucleotide variant
- Location
- chrX:148955833 (GRCh38)
- Structure
- AlphaFold pLDDT 49.27
- Residue 596
- the 'disordered' region
Similar variants
- AFF2 c.3267+5G>C Uncertain significance ★★ same type
- AFF2 p.Ala1197Thr Uncertain significance ★★ ⚠ same type
- AFF2 p.Ala171Pro Uncertain significance ★★ ⚠ same type
- AFF2 p.Arg1238Cys Uncertain significance ★★ ⚠ same type
- AFF2 p.Arg1295Cys Uncertain significance ★★ ⚠ same type
- AFF2 p.Arg670His Uncertain significance ★★ ⚠ same type
- AFF2 p.Asn77Ile Uncertain significance ★★ ⚠ same type
- AFF2 p.Asp187Glu 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/aff2-p-ala596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown