GNAS p.Ala491=
c.1473G>A · rs755184062 · VCV2381279
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00243%, eas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type. | ||
| REVEL | 0.006 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Overall | ||
| CADD | 1.567 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00243%
East Asian · 1/41,078 alleles
Filtering AF
0.000901%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000737%
Overall
0.0013%
20/1,539,102 alleles · very rare
exomes 18/1,387,142 · genomes 2/151,960 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00243% | 41,078 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 60,000 |
| European (non-Finnish) | 0.00148% | 67,574 |
| South Asian | 0.00119% | 84,178 |
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.Ala491=
- Coding
- c.1473G>A
- MANE Select
- NM_000516 · reported on NM_080425
- dbSNP
- rs755184062
- Type
- single nucleotide variant
- Location
- chr20:58854738 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 491
- the 'disordered' region
Similar variants
- GNAS c.432+1G>A Pathogenic ★★ same condition
- GNAS p.Arg265Cys Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg385His Pathogenic ★★ same condition
- GNAS p.Arg42Cys Pathogenic ★★ same condition
- GNAS p.Arg385Cys Uncertain significance ★★ ⚠ same condition
- GNAS p.Asn239Ser Uncertain significance ★★ same condition
- GNAS p.Asp401Asn Uncertain significance ★★ ⚠ same condition
- GNAS p.Pro531Ser Uncertain significance ★★ same condition
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-ala491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown