GNAS p.Arg562=
c.1686C>T · rs747759524 · VCV2577583
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0658%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.061 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 1.2, phastCons 0.1 |
| Overall | ||
| CADD | 11.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0658%
Middle Eastern · 4/6,082 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.0059%
95/1,609,388 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0658% | 1,521 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,921 |
| European (non-Finnish) | 0.00653% | 15,309 |
| Remaining individualsnot grpmax-eligible | 0.00643% | 15,563 |
| Admixed American | 0.00335% | 29,813 |
| Finnishnot grpmax-eligible | 0.00162% | 61,814 |
| South Asian | 0.0011% | 90,792 |
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.Arg562=
- Coding
- c.1686C>T
- MANE Select
- NM_000516 · reported on NM_080425
- dbSNP
- rs747759524
- Type
- single nucleotide variant
- Location
- chr20:58854951 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 562
- the 'disordered' region
Similar variants
- 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
- GNAS p.Ala102Val Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Arg160Cys 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-arg562 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown