GNB5 p.Val375=
c.1125T>C · rs748572863 · VCV1335182
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -1.6 | GERP -4.2 |
| Overall | ||
| CADD | 0.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,008 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000682%
11/1,613,920 alleles · very rare
exomes 10/1,461,692 · genomes 1/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,003 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| European (non-Finnish) | 0.000509% | 196,643 |
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.Val375=
- Coding
- c.1125T>C
- MANE Select
- NM_016194
- dbSNP
- rs748572863
- Type
- single nucleotide variant
- Location
- chr15:52124524 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.92 · 37 PDB
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-val375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown