GNAS p.Lys233=
c.699G>A · rs780331721 · VCV2183479
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.055%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.093 | GERP -2.6, phastCons 0.055 |
| Overall | ||
| CADD | 2.289 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.055%
Admixed American · 33/60,014 alleles
Filtering AF
0.0402%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0351%
Overall
0.00204%
33/1,614,104 alleles · ultra-rare
exomes 31/1,461,882 · genomes 2/152,222 · joint denominator
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.Lys233=
- Coding
- c.699G>A
- MANE Select
- NM_000516
- dbSNP
- rs780331721
- Type
- single nucleotide variant
- Location
- chr20:58909560 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 233
- the 'disordered' region; the g-alpha domain; an α-helix
Similar variants
- GNAS p.Lys233Glu Uncertain significance ★ ⚠ same residue
- GNAS p.Phe233Leu Uncertain significance ⚠ same residue
- GNAS p.Ser233= Likely benign 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
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-lys233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown