Is GNB3 p.Val43= (c.129C>T) pathogenic?

GNB3 p.Val43= (c.129C>T) is classified Likely benign in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). Absent from gnomAD v4.1.

How common is GNB3 p.Val43= (c.129C>T) in the general population?

GNB3 p.Val43= (c.129C>T) is absent from gnomAD v4.1 (gnomAD).

GNB3 p.Val43=

c.129C>T · rs2137981458 · VCV1663471

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.012	GERP -4, phastCons 0.71
Overall
CADD	6.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GNB3
Protein: p.Val43=
Coding: c.129C>T
MANE Select: NM_002075
dbSNP: rs2137981458
Type: single nucleotide variant
Location: chr12:6843002 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 2 PDB

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

Similar variants

GNB3 p.Val43fs Uncertain significance ★ same residue
GNB3 c.203+6G>A Uncertain significance ★★ same type
GNB3 p.Ala106Ser Uncertain significance ★★ ⚠ same type
GNB3 p.Ala231Thr Uncertain significance ★★ ⚠ same type
GNB3 p.Ala64Thr Uncertain significance ★★ ⚠ same type
GNB3 p.Arg129His Uncertain significance ★★ ⚠ same type
GNB3 p.Arg137Gln Uncertain significance ★★ ⚠ same type
GNB3 p.Arg150Cys Uncertain significance ★★ ⚠ same type

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-val43 (accessed [today's date]).

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