AFF3 p.Gly359=
c.1077C>T · VCV4083736
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.44%, sas)
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 0.88 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 8.083 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.44%
South Asian · 1,287/89,190 alleles
Filtering AF
1.38%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.35%
Overall
0.117%
1,877/1,607,538 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.44% | 69 |
| Middle Eastern | 0.215% | 466 |
| Remaining individualsnot grpmax-eligible | 0.12% | 831 |
| Admixed American | 0.0549% | 1,822 |
| European (non-Finnish) | 0.0395% | 2,534 |
| African / African-American | 0.00402% | 24,854 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,472 |
| East Asian | 0.00223% | 44,796 |
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.Gly359=
- Coding
- c.1077C>T
- MANE Select
- NM_001386135
- Type
- single nucleotide variant
- Location
- chr2:99727091 (GRCh38)
- Gene constraint
- LOEUF 0.318 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.20
- Residue 359
- 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-gly359 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown