GNB5 p.Phe254=
c.762C>T · rs144268249 · VCV1210958
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, 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 -0.2 | GERP -4.2, phastCons 0.01 |
| Overall | ||
| CADD | 10.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
Admixed American · 28/59,958 alleles
Filtering AF
0.0332%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0286%
Overall
0.0159%
257/1,613,656 alleles · ultra-rare
exomes 231/1,461,468 · genomes 26/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0467% | 2,141 |
| European (non-Finnish) | 0.0182% | 5,487 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| South Asian | 0.00329% | 30,356 |
| Finnishnot grpmax-eligible | 0.00156% | 64,012 |
| African / African-American | 0.00133% | 74,974 |
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.Phe254=
- Coding
- c.762C>T
- MANE Select
- NM_016194
- dbSNP
- rs144268249
- Type
- single nucleotide variant
- Location
- chr15:52135622 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.92 · 37 PDB
- Residue 254
- a β-strand
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-phe254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown