GNAS p.Pro141=
c.423C>T · VCV4821974
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.64 | GERP -3.9 |
| Overall | ||
| CADD | 3.872 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,088 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,613,584 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,088 |
| European (non-Finnish) | 0.000254% | 393,287 |
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.Pro141=
- Coding
- c.423C>T
- MANE Select
- NM_000516 · reported on NM_080425
- Type
- single nucleotide variant
- Location
- chr20:58853688 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 141
- the 'disordered' region; the g-alpha domain
Similar variants
- GNAS p.Pro141Arg 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
- GNAS c.433-2A>C Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Ala102Thr Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Ala102Val 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-pro141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown