GNB4 p.Ser275=
c.825T>C · VCV4965075
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -14 | GERP -4.3 |
| Overall | ||
| CADD | 0.916 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,884 alleles
Overall
0.000124%
2/1,614,238 alleles · very rare
exomes 2/1,461,860 · genomes 0/152,378 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,884 |
| European (non-Finnish) | 8.47e-05% | 1,180,022 |
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
- GNB4
- Protein
- p.Ser275=
- Coding
- c.825T>C
- MANE Select
- NM_021629
- Type
- single nucleotide variant
- Location
- chr3:179405281 (GRCh38)
- Gene constraint
- LOEUF 0.863 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 97.14
Similar variants
- GNB4 p.Ser275Phe Uncertain significance ★ ⚠ same residue
- GNB4 p.Gly77Arg Pathogenic ★★ same type
- GNB4 p.Lys57Glu Pathogenic/Likely pathogenic ★★ same type
- GNB4 c.497+1G>C Uncertain significance ★★ same type
- GNB4 p.Arg137Ter Uncertain significance ★★ same type
- GNB4 p.Arg15Trp Uncertain significance ★★ ⚠ same type
- GNB4 p.Arg214Ter Uncertain significance ★★ same type
- GNB4 p.Arg22Gln 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/gnb4-p-ser275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown