GNB5 p.Ala84=
c.252G>A · rs35581121 · VCV517014
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 6.85%, mid) — 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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -5.4 |
| Overall | ||
| CADD | 0.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.85%
Middle Eastern · 415/6,060 alleles
Filtering AF
6.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.09%
Overall
3.33%
53,775/1,613,768 alleles · common
exomes 49,753/1,461,448 · genomes 4,022/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 6.85% | 15 |
| European (non-Finnish) | 3.83% | 26 |
| Admixed American | 3.36% | 30 |
| Remaining individualsnot grpmax-eligible | 3.11% | 32 |
| Finnishnot grpmax-eligible | 2.24% | 45 |
| Amishnot grpmax-eligible | 1.86% | 54 |
| South Asian | 1.82% | 55 |
| Ashkenazi Jewishnot grpmax-eligible | 1.79% | 56 |
| African / African-American | 0.689% | 145 |
| East Asian | 0.1% | 997 |
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
- GNB5
- Protein
- p.Ala84=
- Coding
- c.252G>A
- MANE Select
- NM_016194
- dbSNP
- rs35581121
- Type
- single nucleotide variant
- Location
- chr15:52154063 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.92 · 37 PDB
Similar variants
- GNB5 p.Ala84Val Uncertain significance ★ ⚠ same residue
- GNB5 p.Arg288Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- GNB5 p.Ser123Leu Pathogenic ★★ same type
- GNB5 p.Ser123Trp Likely pathogenic ★★ same type
- GNB5 p.Tyr344Ter Pathogenic ★★ same type
- GNB5 p.Ala142Thr Uncertain significance ★★ ⚠ same type
- GNB5 p.Arg98Gly Uncertain significance ★★ ⚠ same type
- GNB5 p.Asn252Ser 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/gnb5-p-ala84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown