Is GNB4 p.Phe151Val (c.451T>G) pathogenic?

GNB4 p.Phe151Val (c.451T>G) is classified Uncertain significance in GNB4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-24). AlphaMissense: likely pathogenic (0.9965); No allele count reported in gnomAD v4.1 (AN 1,609,786); Associated with Charcot-Marie-Tooth disease dominant intermediate F.

What condition is associated with GNB4 p.Phe151Val (c.451T>G)?

GNB4 p.Phe151Val (c.451T>G) is associated with Charcot-Marie-Tooth disease dominant intermediate F (ClinVar).

How common is GNB4 p.Phe151Val (c.451T>G) in the general population?

GNB4 p.Phe151Val (c.451T>G) is no allele count reported in gnomAD v4.1 (AN 1,609,786) (gnomAD).

What do computational predictors say about GNB4 p.Phe151Val (c.451T>G)?

AlphaMissense predicts likely pathogenic (score 0.9965) — an in-silico prediction, not a clinical call.

GNB4 p.Phe151Val

Q: How is Autosomal dominant intermediate Charcot-Marie-Tooth disease type F inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.451T>G · rs2108589504 · VCV1299242

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9965 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,786)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease dominant intermediate F

Computational evidence

Protein change
AlphaMissense	0.9965	likely pathogenic
REVEL	0.832	moderately pathogenic-leaning
SaProt	LLR -13.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 25 kb · p 4.2e-07 · regional, not allelic
Overall
CADD	29.3	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 1,609,786). 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: GNB4
Protein: p.Phe151Val
Coding: c.451T>G
MANE Select: NM_021629
dbSNP: rs2108589504
Type: single nucleotide variant
Location: chr3:179413761 (GRCh38)
Gene constraint: LOEUF 0.863 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 97.14

Full GNB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease dominant intermediate F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant intermediate Charcot-Marie-Tooth disease type F (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

GNB4 p.Gly77Arg Pathogenic ★★ same condition
GNB4 p.Lys57Glu Pathogenic/Likely pathogenic ★★ same condition
GNB4 c.497+1G>C Uncertain significance ★★ same condition
GNB4 p.Arg137Ter Uncertain significance ★★ same condition
GNB4 p.Arg15Trp Uncertain significance ★★ ⚠ same condition
GNB4 p.Arg214Ter Uncertain significance ★★ same condition
GNB4 p.Arg22Gln Uncertain significance ★★ ⚠ same condition
GNB4 p.Arg251Gln Uncertain significance ★★ ⚠ same condition

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/gnb4-p-phe151val (accessed [today's date]).

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