GNAS p.Ala102=
c.306G>A · rs117849691 · VCV435342
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.394%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.038 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP -3.4, phastCons 0.99 |
| Overall | ||
| CADD | 9.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.394%
African / African-American · 296/75,032 alleles
Filtering AF
0.358%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.343%
Overall
0.0258%
417/1,614,116 alleles · rare
exomes 234/1,461,818 · genomes 183/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.394% | 253 |
| Middle Eastern | 0.066% | 1,515 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,718 |
| Admixed American | 0.035% | 2,858 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,401 |
| European (non-Finnish) | 0.00551% | 18,153 |
| South Asian | 0.00329% | 30,361 |
| East Asian | 0.00223% | 44,882 |
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.Ala102=
- Coding
- c.306G>A
- MANE Select
- NM_000516
- dbSNP
- rs117849691
- Type
- single nucleotide variant
- Location
- chr20:58903579 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 102
- the 'disordered' region; the g-alpha domain; an α-helix
Similar variants
- GNAS p.Ala102Thr Pathogenic/Likely pathogenic ★★ same residue
- GNAS p.Ala102Val Pathogenic/Likely pathogenic ★★ same residue
- GNAS p.Glu102Gln Uncertain significance ★ same residue
- GNAS p.Met102fs 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
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-ala102 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown