Is MPZ p.Phe176fs (c.527_537del) pathogenic?

MPZ p.Phe176fs (c.527537del) is classified Pathogenic in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Phe176fs (c.527_537del)?

MPZ p.Phe176fs (c.527_537del) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

MPZ p.Phe176fs

c.527_537del · VCV3651974

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MPZ
Protein: p.Phe176fs
Coding: c.527_537del
MANE Select: NM_000530
Type: Deletion
Location: chr1:161306376 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB

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

Similar variants

MPZ p.Phe176Leu Uncertain significance ★ same residue
MPZ p.Asp104fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Ile162fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Leu144fs Pathogenic ★★ same condition
MPZ p.Pro26fs Pathogenic ★★ same condition
MPZ p.Ser44fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Ser63del Pathogenic ★★ same condition
MPZ p.Tyr145fs 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-phe176fs (accessed [today's date]).

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