GNB1 p.Ser74=
c.222G>A · rs545209841 · VCV1898007
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
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 -11 | GERP -5.2 |
| Overall | ||
| CADD | 1.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/90,738 alleles
Filtering AF
0.0128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00205%
33/1,609,530 alleles · ultra-rare
exomes 33/1,457,270 · genomes 0/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,041 |
| Admixed American | 0.00334% | 29,977 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,183 |
| East Asian | 0.00223% | 44,862 |
| European (non-Finnish) | 0.00085% | 117,609 |
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
- GNB1
- Protein
- p.Ser74=
- Coding
- c.222G>A
- MANE Select
- NM_002074
- dbSNP
- rs545209841
- Type
- single nucleotide variant
- Location
- chr1:1806520 (GRCh38)
- Gene constraint
- LOEUF 0.222 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 97.04 · 1043 PDB
- Residue 74
- a β-strand
Similar variants
- GNB1 p.Ser74Leu Pathogenic ★ same residue
- GNB1 c.498-2A>G Likely pathogenic ★★ same type
- GNB1 p.Ala73Ser Pathogenic/Likely pathogenic ★★ same type
- GNB1 p.Ala73Thr Pathogenic/Likely pathogenic ★★ same type
- GNB1 p.Ala92Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- GNB1 p.Asp118Gly Pathogenic ★★ same type
- GNB1 p.Asp118His Likely pathogenic ★★ same type
- GNB1 p.Asp118Tyr Pathogenic ★★ 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/gnb1-p-ser74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown