GNAS p.Ala256=
c.768G>C · rs762642543 · VCV3033056
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.067%, sas)
Conditions
1
GNAS-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.023 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.95 | GERP 1.6, phastCons 0.001 |
| Overall | ||
| CADD | 10.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.067%
South Asian · 61/90,978 alleles
Filtering AF
0.0535%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0486%
Overall
0.00435%
70/1,610,954 alleles · ultra-rare
exomes 67/1,458,724 · genomes 3/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.067% | 1,491 |
| Middle Eastern | 0.0165% | 6,078 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,772 |
| European (non-Finnish) | 0.000424% | 235,896 |
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.Ala256=
- Coding
- c.768G>C
- MANE Select
- NM_000516 · reported on NM_080425
- dbSNP
- rs762642543
- Type
- single nucleotide variant
- Location
- chr20:58854033 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 256
- the g-alpha domain; the 'disordered' region
Similar variants
- GNAS p.Ala102Val Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg165His Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg201Cys Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg258Gln Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg42His Likely pathogenic ★★ same condition
- GNAS p.Gln12Ter Pathogenic ★★ same condition
- GNAS p.Gln213Ter Pathogenic ★★ same condition
- GNAS p.Gln31Ter Pathogenic ★★ 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-ala256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown