GNB3 p.Ala11=
c.33G>A · rs566098814 · VCV1151061
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0119%, 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 -1.5 | GERP -4.3 |
| Overall | ||
| CADD | 9.349 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0119%
European (non-Finnish) · 140/1,179,750 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00964%
Overall
0.01%
162/1,613,584 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0119% | 8,427 |
| African / African-American | 0.00933% | 10,721 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,495 |
| South Asian | 0.0066% | 15,151 |
| Admixed American | 0.005% | 19,983 |
| East Asian | 0.00223% | 44,872 |
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
- GNB3
- Protein
- p.Ala11=
- Coding
- c.33G>A
- MANE Select
- NM_002075
- dbSNP
- rs566098814
- Type
- single nucleotide variant
- Location
- chr12:6841320 (GRCh38)
- Gene constraint
- LOEUF 1.072 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.19 · 2 PDB
Similar variants
- GNB3 p.Ala11Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- GNB3 c.203+6G>A Uncertain significance ★★ same type
- GNB3 p.Ala106Ser Uncertain significance ★★ ⚠ same type
- GNB3 p.Ala231Thr Uncertain significance ★★ ⚠ same type
- GNB3 p.Ala64Thr Uncertain significance ★★ ⚠ same type
- GNB3 p.Arg129His Uncertain significance ★★ ⚠ same type
- GNB3 p.Arg137Gln Uncertain significance ★★ ⚠ same type
- GNB3 p.Arg150Cys 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/gnb3-p-ala11 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown