GNAS p.Val36=
c.108C>T · rs146581290 · VCV287727
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.053%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 13.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.053%
Middle Eastern · 2/3,772 alleles
Filtering AF
0.00937%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00393%
Overall
0.00409%
52/1,271,636 alleles · ultra-rare
exomes 46/1,125,500 · genomes 6/146,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.053% | 1,886 |
| Remaining individualsnot grpmax-eligible | 0.0122% | 8,203 |
| European (non-Finnish) | 0.00423% | 23,634 |
| South Asian | 0.00385% | 26,002 |
| African / African-American | 0.00159% | 62,794 |
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.Val36=
- Coding
- c.108C>T
- MANE Select
- NM_000516
- dbSNP
- rs146581290
- Type
- single nucleotide variant
- Location
- chr20:58891834 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 36
- an α-helix; the 'disordered' region
Similar variants
- GNAS p.Val36Ile Uncertain significance ★★ same residue
- GNAS p.Ala36Glu 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
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-val36 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown