Is GNB1 p.Phe234Leu (c.700T>C) pathogenic?

GNB1 p.Phe234Leu (c.700T>C) is classified Uncertain significance in GNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely pathogenic (0.9951); No allele count reported in gnomAD v4.1 (AN 1,575,826).

How common is GNB1 p.Phe234Leu (c.700T>C) in the general population?

GNB1 p.Phe234Leu (c.700T>C) is no allele count reported in gnomAD v4.1 (AN 1,575,826) (gnomAD).

What do computational predictors say about GNB1 p.Phe234Leu (c.700T>C)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

GNB1 p.Phe234Leu

c.700T>C · rs2522194237 · VCV2837934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,575,826)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic
REVEL	0.669	pathogenic-leaning
SaProt	LLR -11.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 29 kb · p 7e-38 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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 1,575,826). 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: GNB1
Protein: p.Phe234Leu
Coding: c.700T>C
MANE Select: NM_002074
dbSNP: rs2522194237
Type: single nucleotide variant
Location: chr1:1789269 (GRCh38)
Gene constraint: LOEUF 0.222 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 97.04 · 1043 PDB
Residue 234: a β-strand

Full GNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GNB1 c.498-2A>G Likely pathogenic ★★ same type
GNB1 p.Ala73Ser Pathogenic/Likely pathogenic ★★ same type
GNB1 p.Ala73Thr Pathogenic/Likely pathogenic ★★ same type
GNB1 p.Ala92Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
GNB1 p.Asp118Gly Pathogenic ★★ same type
GNB1 p.Asp118His Likely pathogenic ★★ same type
GNB1 p.Asp118Tyr Pathogenic ★★ same type
GNB1 p.Asp76Asn Pathogenic/Likely pathogenic ★★ 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/gnb1-p-phe234leu (accessed [today's date]).

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