GNAS p.Arg201Ser
c.601C>A · rs11554273 · VCV15937
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9995 | likely pathogenic · top 2% in GNAS |
|---|---|---|
| REVEL | 0.967 | strongly pathogenic-leaning |
| SaProt | LLR -16.02 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 0.88, phastCons 1 |
| Regional constraint | o/e 0.31 | constrained · MANE · 18 kb · p 9.1e-28 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R844S vs ClinVar R201S) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.00156% | 64,018 |
| European (non-Finnish)grpmax | 0.000254% | 393,201 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg201Ser
- Coding
- c.601C>A
- MANE Select
- NM_000516
- dbSNP
- rs11554273
- Type
- single nucleotide variant
- Location
- chr20:58909365 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 201
- the 'disordered' region; a binding site; a modified residue (adp-ribosylarginine; by cholera toxin); the g-alpha domain; a UniProt-annotated variant site (in mas; also found in somatotrophinoma); a UniProt-annotated variant site (in mas); a UniProt-annotated variant site (in mas and aimah1; also found in somatotrophinoma); a UniProt-annotated variant site (in non-mas endocrine tumors); a UniProt-annotated variant site (in aimah1; also found in pituitary tumor and polyostotic fibrous dysplasia); the 'g2 motif' region; a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)
Disease context
McCune-Albright syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: ACTH-independent macronodular adrenal hyperplasia 1
For McCune-Albright syndrome (Orphanet):
- Inheritance
- Not applicable
- Onset
- Childhood
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- GNAS p.Arg201Cys Pathogenic/Likely pathogenic ★★ same residue
- GNAS p.Arg201His Pathogenic/Likely pathogenic ★★ same residue
- GNAS p.Arg201Gly Pathogenic same residue
- GNAS c.433-2A>C Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg231Cys Pathogenic/Likely pathogenic ★★ same condition
- GNAS p.Arg342Ter Pathogenic ★★ same condition
- GNAS p.Gln12Ter Pathogenic ★★ same condition
- GNAS p.Gln29Ter 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-arg201ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown