Is GNB3 p.Arg256= (c.766C>A) pathogenic?

GNB3 p.Arg256= (c.766C>A) is classified Likely benign in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). Ultra-rare (popmax 0.0582%, sas).

How common is GNB3 p.Arg256= (c.766C>A) in the general population?

GNB3 p.Arg256= (c.766C>A) is ultra-rare (popmax 0.0582%, sas) (gnomAD).

GNB3 p.Arg256=

c.766C>A · rs782167184 · VCV1130850

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, sas)

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 2.9	GERP 0.34, phastCons 1
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0582% South Asian · 53/91,082 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00384% 62/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0582%	1,719
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.000508%	196,665

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.Arg256=
Coding: c.766C>A
MANE Select: NM_031299 · reported on NM_002075
dbSNP: rs782167184
Type: single nucleotide variant
Location: chr12:6845652 (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-arg256 (accessed [today's date]).

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