Is GNB3 p.Leu336Val (c.1006C>G) pathogenic?

GNB3 p.Leu336Val (c.1006C>G) is classified Uncertain significance in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-02). AlphaMissense: ambiguous (0.5466); No allele count reported in gnomAD v4.1 (AN 1,588,800).

How common is GNB3 p.Leu336Val (c.1006C>G) in the general population?

GNB3 p.Leu336Val (c.1006C>G) is no allele count reported in gnomAD v4.1 (AN 1,588,800) (gnomAD).

What do computational predictors say about GNB3 p.Leu336Val (c.1006C>G)?

AlphaMissense predicts ambiguous (score 0.5466) — an in-silico prediction, not a clinical call.

GNB3 p.Leu336Val

c.1006C>G · rs2137996004 · VCV1348903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5466 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,800)

Computational evidence

Protein change
AlphaMissense	0.5466	ambiguous
REVEL	0.296	indeterminate
SaProt	LLR -10.94	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 5,607 bp · p 0.03 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,588,800). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GNB3
Protein: p.Leu336Val
Coding: c.1006C>G
MANE Select: NM_031299 · reported on NM_002075
dbSNP: rs2137996004
Type: single nucleotide variant
Location: chr12:6846881 (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-leu336val (accessed [today's date]).

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