Is GNB3 p.Phe335= (c.1005C>T) pathogenic?

GNB3 p.Phe335= (c.1005C>T) is classified Likely benign in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-22). Absent from gnomAD v4.1.

How common is GNB3 p.Phe335= (c.1005C>T) in the general population?

GNB3 p.Phe335= (c.1005C>T) is absent from gnomAD v4.1 (gnomAD).

GNB3 p.Phe335=

c.1005C>T · rs782320266 · VCV1919362

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.
REVEL	0.22	benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 1.5, phastCons 1
Overall
CADD	11.2	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.Phe335=
Coding: c.1005C>T
MANE Select: NM_031299 · reported on NM_002075
dbSNP: rs782320266
Type: single nucleotide variant
Location: chr12:6846880 (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-phe335 (accessed [today's date]).

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