Is GNB3 p.Asp254= (c.762C>T) pathogenic?

GNB3 p.Asp254= (c.762C>T) is classified Benign in GNB3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 9.77%, amr) — too common for a highly-penetrant pathogenic allele.

GNB3 p.Asp254=

Q: How common is GNB3 p.Asp254= (c.762C>T) in the general population?

GNB3 p.Asp254= (c.762C>T) is common (popmax 9.77%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.762C>T · rs2234757 · VCV1169656

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 9.77%, amr) — too common for a highly-penetrant pathogenic allele

⚠ 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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.8	GERP 1.5, phastCons 1
Overall
CADD	13.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.77% Admixed American · 5,867/60,028 alleles

Filtering AF 9.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.48%

Overall 0.567% 9,151/1,613,990 alleles · common exomes 7,437/1,461,666 · genomes 1,714/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.77%	10
East Asian	3.94%	25
African / African-American	0.786%	127
Remaining individualsnot grpmax-eligible	0.619%	162
South Asian	0.318%	314
Ashkenazi Jewishnot grpmax-eligible	0.138%	722
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.0169%	5,900

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.Asp254=
Coding: c.762C>T
MANE Select: NM_002075
dbSNP: rs2234757
Type: single nucleotide variant
Location: chr12:6845648 (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-asp254 (accessed [today's date]).

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