GNAS p.Ala480=
c.1440T>A · rs548840457 · VCV3037976
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.106%, afr)
Conditions
1
GNAS-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.004 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -2.1 |
| Overall | ||
| CADD | 1.256 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.106%
African / African-American · 77/72,602 alleles
Filtering AF
0.087%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.08%
Overall
0.00548%
84/1,531,508 alleles · rare
exomes 47/1,379,442 · genomes 37/152,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.106% | 943 |
| Remaining individualsnot grpmax-eligible | 0.0067% | 14,926 |
| Admixed American | 0.00593% | 16,874 |
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.Ala480=
- Coding
- c.1440T>A
- MANE Select
- NM_000516 · reported on NM_080425
- dbSNP
- rs548840457
- Type
- single nucleotide variant
- Location
- chr20:58854705 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 480
- 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-ala480 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown