GNB5 p.Ser199=
c.597G>A · VCV4873802
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0535%, eas)
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 -12 | GERP -3.9 |
| Overall | ||
| CADD | 1.986 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0535%
East Asian · 24/44,892 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0313%
Overall
0.00335%
54/1,613,904 alleles · ultra-rare
exomes 51/1,461,842 · genomes 3/152,062 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0535% | 1,871 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 0.00229% | 43,704 |
| African / African-American | 0.00134% | 74,882 |
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.Ser199=
- Coding
- c.597G>A
- MANE Select
- NM_016194
- Type
- single nucleotide variant
- Location
- chr15:52141170 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.92 · 37 PDB
- Residue 199
- a β-strand
Similar variants
- GNB5 p.Ser199Leu 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-ser199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown