Is GNAS p.Arg317= (c.951C>T) pathogenic?

GNAS p.Arg317= (c.951C>T) is classified Benign/Likely benign in GNAS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Low-frequency (popmax 2.22%, afr); Associated with McCune-Albright syndrome.

What condition is associated with GNAS p.Arg317= (c.951C>T)?

GNAS p.Arg317= (c.951C>T) is associated with McCune-Albright syndrome, pseudohypoparathyroidism type 1A, progressive osseous heteroplasia (ClinVar).

How common is GNAS p.Arg317= (c.951C>T) in the general population?

GNAS p.Arg317= (c.951C>T) is low-frequency (popmax 2.22%, afr) (gnomAD).

How is McCune-Albright syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

GNAS p.Arg317=

c.951C>T · rs75561530 · VCV722980

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.22%, afr)

Conditions

McCune-Albright syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.78 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 0.84, phastCons 1
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.22% African / African-American · 1,668/75,002 alleles

Filtering AF 2.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1%

Overall 0.115% 1,854/1,613,790 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.22%	45
Remaining individualsnot grpmax-eligible	0.15%	665
Admixed American	0.117%	858
Middle Eastern	0.0495%	2,021
South Asian	0.00549%	18,213
European (non-Finnish)	0.00119%	84,264

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.Arg317=
Coding: c.951C>T
MANE Select: NM_000516
dbSNP: rs75561530
Type: single nucleotide variant
Location: chr20:58910062 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.47 · 200 PDB
Residue 317: an α-helix; the g-alpha domain; the 'disordered' region

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

Disease context

McCune-Albright syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudohypoparathyroidism type 1A progressive osseous heteroplasia pseudohypoparathyroidism type 1B pseudohypoparathyroidism type 1C pseudopseudohypoparathyroidism ACTH-independent macronodular adrenal hyperplasia 1 pituitary adenoma 3, multiple types

For McCune-Albright syndrome (Orphanet):

Inheritance: Not applicable
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GNAS p.Arg317His Uncertain significance ★ ⚠ same residue
GNAS p.Arg317Gly Uncertain significance ★ same residue
GNAS p.Arg317Leu Uncertain significance ★ ⚠ same residue
GNAS c.139+1G>C Pathogenic ★★ same condition
GNAS c.432+1G>A Pathogenic ★★ same condition
GNAS c.433-2A>C Pathogenic/Likely pathogenic ★★ same condition
GNAS p.Arg165Cys Pathogenic ★★ same condition
GNAS p.Arg201Cys Pathogenic/Likely 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-arg317 (accessed [today's date]).

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