Is GNB3 p.Asp323= (c.969C>T) pathogenic?

GNB3 p.Asp323= (c.969C>T) is classified Likely benign in GNB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0214%, afr).

How common is GNB3 p.Asp323= (c.969C>T) in the general population?

GNB3 p.Asp323= (c.969C>T) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

GNB3 p.Asp323=

c.969C>T · rs373634972 · VCV1158787

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.115	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.3	GERP -5.1
Overall
CADD	9.435	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,844 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00237% 38/1,602,462 alleles · ultra-rare exomes 26/1,450,270 · genomes 12/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0214%	4,678
Admixed American	0.00858%	11,654
Remaining individualsnot grpmax-eligible	0.00322%	31,059
South Asian	0.00226%	44,302
East Asian	0.00224%	44,606
European (non-Finnish)	0.00102%	97,881

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: GNB3
Protein: p.Asp323=
Coding: c.969C>T
MANE Select: NM_002075
dbSNP: rs373634972
Type: single nucleotide variant
Location: chr12:6846844 (GRCh38)

Full GNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/gnb3-p-asp323 (accessed [today's date]).

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