Is MPZ p.Val38Phe (c.112G>T) pathogenic?

MPZ p.Val38Phe (c.112G>T) is classified Uncertain significance in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-30). AlphaMissense: ambiguous (0.4807); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease dominant intermediate D.

What condition is associated with MPZ p.Val38Phe (c.112G>T)?

MPZ p.Val38Phe (c.112G>T) is associated with Charcot-Marie-Tooth disease dominant intermediate D (ClinVar).

How common is MPZ p.Val38Phe (c.112G>T) in the general population?

MPZ p.Val38Phe (c.112G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPZ p.Val38Phe (c.112G>T)?

AlphaMissense predicts ambiguous (score 0.4807) — an in-silico prediction, not a clinical call.

MPZ p.Val38Phe

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

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

c.112G>T · rs2102260135 · VCV1676219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4807 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease dominant intermediate D

Computational evidence

Protein change
AlphaMissense	0.4807	ambiguous
REVEL	0.518	indeterminate
SaProt	LLR -11.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.88, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	24.1	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

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: MPZ
Protein: p.Val38Phe
Coding: c.112G>T
MANE Select: NM_000530
dbSNP: rs2102260135
Type: single nucleotide variant
Location: chr1:161307380 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 38: a β-strand; the ig-like v-type domain

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

Disease context

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

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

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

MPZ p.Val38Asp Likely pathogenic ★ same residue
MPZ p.Val38= Likely benign ★ same residue
MPZ p.Arg227Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
MPZ p.Asp35Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
MPZ p.Gly167Arg Pathogenic ★★ same condition
MPZ p.Gly85Ter Pathogenic/Likely pathogenic ★★ same condition
MPZ p.His81Arg Pathogenic ★★ ⚠ same condition
MPZ p.Pro133Ala Likely pathogenic ★★ 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/mpz-p-val38phe (accessed [today's date]).

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