GNB3 p.Arg219=
c.657T>A · rs45476395 · VCV784297
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.18%, nfe)
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 -0.14 | GERP -5.1, phastCons 0.35 |
| Overall | ||
| CADD | 8.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.18%
European (non-Finnish) · 13,976/1,179,794 alleles
Filtering AF
1.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.16%
Overall
0.945%
15,256/1,613,680 alleles · low-frequency
exomes 14,304/1,461,684 · genomes 952/151,996 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.18% | 84 |
| Admixed American | 0.87% | 115 |
| Remaining individualsnot grpmax-eligible | 0.771% | 130 |
| Middle Eastern | 0.215% | 466 |
| African / African-American | 0.16% | 624 |
| Finnishnot grpmax-eligible | 0.153% | 653 |
| Ashkenazi Jewishnot grpmax-eligible | 0.108% | 925 |
| South Asian | 0.0143% | 7,005 |
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
- GNB3
- Protein
- p.Arg219=
- Coding
- c.657T>A
- MANE Select
- NM_002075
- dbSNP
- rs45476395
- Type
- single nucleotide variant
- Location
- chr12:6843936 (GRCh38)
- Gene constraint
- LOEUF 1.072 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.19 · 2 PDB
Similar variants
- GNB3 p.Arg219Cys Uncertain significance ★ ⚠ same residue
- GNB3 p.Arg219His Uncertain significance ★ ⚠ same residue
- GNB3 c.203+6G>A Uncertain significance ★★ same type
- GNB3 p.Ala106Ser Uncertain significance ★★ ⚠ same type
- GNB3 p.Ala231Thr Uncertain significance ★★ ⚠ same type
- GNB3 p.Ala64Thr Uncertain significance ★★ ⚠ same type
- GNB3 p.Arg129His Uncertain significance ★★ ⚠ same type
- GNB3 p.Arg137Gln 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/gnb3-p-arg219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown