GNAS p.Ala508=
c.1524C>T · rs111796234 · VCV1328360
Conflicting classifications of pathogenicity
No assertion criteria
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0664%, mid)
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 -2.8 | GERP -2.5 |
| Overall | ||
| CADD | 3.102 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0664%
Middle Eastern · 4/6,020 alleles
Filtering AF
0.0226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00864%
136/1,574,472 alleles · ultra-rare
exomes 115/1,422,460 · genomes 21/152,012 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0664% | 1,505 |
| Remaining individualsnot grpmax-eligible | 0.0228% | 4,376 |
| Admixed American | 0.014% | 7,149 |
| European (non-Finnish) | 0.00917% | 10,911 |
| African / African-American | 0.00404% | 24,771 |
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.Ala508=
- Coding
- c.1524C>T
- MANE Select
- NM_000516 · reported on NM_080425
- dbSNP
- rs111796234
- Type
- single nucleotide variant
- Location
- chr20:58854789 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 508
- 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-ala508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown