Is GNAS p.Val323= (c.969C>T) pathogenic?

GNAS p.Val323= (c.969C>T) is classified Likely benign in GNAS (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-05). Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with GNAS p.Val323= (c.969C>T)?

GNAS p.Val323= (c.969C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GNAS p.Val323= (c.969C>T) in the general population?

GNAS p.Val323= (c.969C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

GNAS p.Val323=

c.969C>T · rs189777461 · VCV2282455

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.139	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.8, phastCons 1
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/75,078 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000744% 12/1,613,322 alleles · ultra-rare exomes 6/1,460,964 · genomes 6/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,385
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	8.48e-05%	1,179,851

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.Val323=
Coding: c.969C>T
MANE Select: NM_000516 · reported on NM_080425
dbSNP: rs189777461
Type: single nucleotide variant
Location: chr20:58854234 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.47 · 200 PDB
Residue 323: a β-strand; the g-alpha domain; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNAS p.Asp323His Uncertain significance ⚠ same residue
GNAS c.432+1G>A Pathogenic ★★ same condition
GNAS p.Arg265Cys Pathogenic/Likely pathogenic ★★ same condition
GNAS p.Arg385His Pathogenic ★★ same condition
GNAS p.Arg42Cys Pathogenic ★★ same condition
GNAS p.Arg385Cys Uncertain significance ★★ ⚠ same condition
GNAS p.Asn239Ser Uncertain significance ★★ same condition
GNAS p.Asp401Asn Uncertain significance ★★ ⚠ 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-val323 (accessed [today's date]).

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