GNAS p.Arg217=
c.651T>A · rs75176432 · VCV783077
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.145 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 6.073 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
European (non-Finnish) · 11,997/1,179,494 alleles
Filtering AF
1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.996%
Overall
0.837%
13,445/1,606,668 alleles · low-frequency
exomes 12,458/1,454,602 · genomes 987/152,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.02% | 98 |
| Admixed American | 0.96% | 104 |
| Remaining individualsnot grpmax-eligible | 0.813% | 123 |
| Ashkenazi Jewishnot grpmax-eligible | 0.46% | 217 |
| African / African-American | 0.192% | 520 |
| Middle Eastern | 0.165% | 605 |
| Finnishnot grpmax-eligible | 0.121% | 825 |
| East Asian | 0.0067% | 14,935 |
| South Asian | 0.0044% | 22,741 |
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
- GNAS
- Protein
- p.Arg217=
- Coding
- c.651T>A
- MANE Select
- NM_000516 · reported on NM_016592
- dbSNP
- rs75176432
- Type
- single nucleotide variant
- Location
- chr20:58840757 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 217
- the 'disordered' region; the g-alpha domain; a β-strand
Similar variants
- GNAS p.Val217= Uncertain significance ★ same residue
- GNAS c.139+1G>C Pathogenic ★★ same type
- GNAS c.139+2T>C Pathogenic ★★ same type
- GNAS c.312+5G>A Pathogenic ★★ same type
- GNAS c.432+1G>A Pathogenic ★★ same type
- GNAS c.433-2A>C Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Ala102Thr Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Ala102Val Pathogenic/Likely 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/gnas-p-arg217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown