GNB5 p.Pro175=
c.525C>T · VCV4683980
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.021%, 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 -2.1 | GERP -3.4 |
| Overall | ||
| CADD | 4.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.021%
European (non-Finnish) · 248/1,179,762 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.018%
Overall
0.0162%
262/1,613,812 alleles · ultra-rare
exomes 247/1,461,600 · genomes 15/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.021% | 4,757 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,929 |
| African / African-American | 0.00533% | 18,748 |
| Admixed American | 0.005% | 20,005 |
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.Pro175=
- Coding
- c.525C>T
- MANE Select
- NM_016194
- Type
- single nucleotide variant
- Location
- chr15:52141242 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.92 · 37 PDB
- Residue 175
- an α-helix
Similar variants
- 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
- GNB5 p.Asn345Ser 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-pro175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown