GNB1 p.Phe222=
c.666C>T · rs2100502987 · VCV1568852
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.118 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 6.729 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,854 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,613,990 alleles · very rare
exomes 2/1,461,684 · genomes 0/152,306 · joint denominator
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.Phe222=
- Coding
- c.666C>T
- MANE Select
- NM_002074
- dbSNP
- rs2100502987
- Type
- single nucleotide variant
- Location
- chr1:1790428 (GRCh38)
- Gene constraint
- LOEUF 0.222 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 97.04 · 1043 PDB
- Residue 222
- a β-strand
Similar variants
- GNB1 p.Phe222Val Likely benign ★ 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-phe222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown