Is MPZ p.Val92= (c.276G>A) pathogenic?

MPZ p.Val92= (c.276G>A) is classified Pathogenic in MPZ (ClinVar, Single submitter, 3 submitters; last evaluated 2025-05-05). Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Val92= (c.276G>A)?

MPZ p.Val92= (c.276G>A) is associated with Charcot-Marie-Tooth disease type 1, Charcot-Marie-Tooth disease type 1B, Charcot-Marie-Tooth disease (ClinVar).

How common is MPZ p.Val92= (c.276G>A) in the general population?

MPZ p.Val92= (c.276G>A) is absent from gnomAD v4.1 (gnomAD).

MPZ p.Val92=

c.276G>A · rs1558154193 · VCV14200

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.40	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.8	GERP 0.67, phastCons 1
Overall
CADD	18.51	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: MPZ
Protein: p.Val92=
Coding: c.276G>A
MANE Select: NM_000530
dbSNP: rs1558154193
Type: single nucleotide variant
Location: chr1:161306880 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 92: a β-strand; a UniProt-annotated variant site (in cmt2i; patient carrying also asn-89 and met-162); 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 type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 1B Charcot-Marie-Tooth disease

Similar variants

MPZ p.Val92Glu Uncertain significance ★★ ⚠ same residue
MPZ p.Val92Met Uncertain significance ★★ ⚠ same residue
MPZ c.235-1G>T Pathogenic/Likely pathogenic ★★ same condition
MPZ c.448+1G>A Pathogenic/Likely pathogenic ★★ same condition
MPZ c.448+1G>T Likely pathogenic ★★ same condition
MPZ c.448+2T>G Likely pathogenic ★★ same condition
MPZ c.584+2T>G Pathogenic ★★ same condition
MPZ c.68-1G>A Pathogenic/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-val92 (accessed [today's date]).

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