GNAS p.Arg38=
c.114G>A · rs770697642 · VCV1112346
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0181%, amr)
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 3 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 12.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0181%
Admixed American · 8/44,232 alleles
Filtering AF
0.00895%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00649%
Overall
0.00129%
16/1,244,444 alleles · ultra-rare
exomes 14/1,098,378 · genomes 2/146,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0181% | 5,529 |
| African / African-American | 0.0016% | 62,482 |
| South Asian | 0.00139% | 72,156 |
| European (non-Finnish) | 0.000629% | 159,000 |
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.Arg38=
- Coding
- c.114G>A
- MANE Select
- NM_000516
- dbSNP
- rs770697642
- Type
- single nucleotide variant
- Location
- chr20:58891840 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 38
- an α-helix; the 'disordered' region
Similar variants
- GNAS p.Arg38Trp Uncertain significance ★★ same residue
- GNAS p.Arg38Pro Uncertain significance ★ same residue
- GNAS p.Ser38= Likely benign same residue
- GNAS p.Arg38fs Pathogenic 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
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-arg38 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown