Is GNAS p.Cys3= (c.9C>T) pathogenic?

GNAS p.Cys3= (c.9C>T) is classified Benign/Likely benign in GNAS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.862%, eas).

How common is GNAS p.Cys3= (c.9C>T) in the general population?

GNAS p.Cys3= (c.9C>T) is rare (popmax 0.862%, eas) (gnomAD).

GNAS p.Cys3=

c.9C>T · rs200810763 · VCV779991

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.862%, eas)

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 -0.38	GERP -3, phastCons 0.35
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.862% East Asian · 119/13,812 alleles

Filtering AF 0.736% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.688%

Overall 0.0706% 835/1,182,296 alleles · rare exomes 732/1,036,548 · genomes 103/145,748 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.862%	116
Remaining individualsnot grpmax-eligible	0.148%	674
European (non-Finnish)	0.0702%	1,424
Middle Eastern	0.0337%	2,964
African / African-American	0.0113%	8,827
Admixed American	0.00973%	10,273
South Asian	0.00181%	55,298

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.Cys3=
Coding: c.9C>T
MANE Select: NM_000516
dbSNP: rs200810763
Type: single nucleotide variant
Location: chr20:58891735 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.47 · 200 PDB
Residue 3: the 'disordered' region

Full GNAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GNAS p.Cys3Arg Likely pathogenic ★ same residue
GNAS p.Cys3Ser Pathogenic ★ same residue
GNAS p.Arg3Gly Uncertain significance ★ same residue
GNAS p.Arg3Trp Uncertain significance ★ 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-cys3 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown