Is GNB3 p.Leu284= (c.852A>G) pathogenic?

GNB3 p.Leu284= (c.852A>G) is classified Benign/Likely benign in GNB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-24). Rare (popmax 0.277%, sas).

How common is GNB3 p.Leu284= (c.852A>G) in the general population?

GNB3 p.Leu284= (c.852A>G) is rare (popmax 0.277%, sas) (gnomAD).

GNB3 p.Leu284=

c.852A>G · rs782316014 · VCV1167865

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.277%, 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 6	GERP -2.3, phastCons 1
Overall
CADD	8.933	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.277% South Asian · 252/91,080 alleles

Filtering AF 0.249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.238%

Overall 0.0164% 265/1,614,066 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.277%	361
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,060
European (non-Finnish)	8.47e-05%	1,179,979

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.Leu284=
Coding: c.852A>G
MANE Select: NM_031299 · reported on NM_002075
dbSNP: rs782316014
Type: single nucleotide variant
Location: chr12:6845738 (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-leu284 (accessed [today's date]).

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