GNAS p.Arg16=
c.48C>G · rs1452728127 · VCV3031100
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00244%, eas)
Conditions
1
GNAS-related disorder
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 4.3 | GERP 0.45, phastCons 1 |
| Overall | ||
| CADD | 18.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00244%
East Asian · 1/40,920 alleles
Filtering AF
0.000786%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000623%
Overall
0.00103%
16/1,550,118 alleles · very rare
exomes 16/1,397,798 · genomes 0/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00244% | 40,920 |
| European (non-Finnish) | 0.00131% | 76,436 |
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.Arg16=
- Coding
- c.48C>G
- MANE Select
- NM_000516 · reported on NM_080425
- dbSNP
- rs1452728127
- Type
- single nucleotide variant
- Location
- chr20:58853313 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 16
- the 'disordered' region; an α-helix
Similar variants
- GNAS p.Glu16Lys Uncertain significance ★ same residue
- 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
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-arg16 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown