Is MPZ p.Arg67fs (c.200_201del) pathogenic?

MPZ p.Arg67fs (c.200201del) is classified Pathogenic/Likely pathogenic in MPZ (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-15). No gnomAD frequency available for this variant; Associated with MPZ-related disorder.

What condition is associated with MPZ p.Arg67fs (c.200_201del)?

MPZ p.Arg67fs (c.200_201del) is associated with MPZ-related disorder, Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Arg67fs (c.200_201del) in the general population?

MPZ p.Arg67fs (c.200_201del) is no gnomAD frequency available for this variant (gnomAD).

MPZ p.Arg67fs

c.200_201del · rs1670284480 · VCV917144

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

MPZ-related disorder

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 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: MPZ
Protein: p.Arg67fs
Coding: c.200_201del
MANE Select: NM_000530
dbSNP: rs1670284480
Type: Microsatellite
Location: chr1:161307291 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 67: 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

MPZ-related disorder

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

Similar variants

MPZ p.Arg67Cys Uncertain significance ★★ ⚠ same residue
MPZ p.Arg67Pro Likely pathogenic ★ same residue
MPZ p.Arg67His Conflicting classifications of pathogenicity ★ ⚠ same residue
MPZ p.Arg67= Likely benign ★ same residue
MPZ p.Ala189fs Pathogenic ★★ same condition
MPZ c.585-7_585-5del Conflicting classifications of pathogenicity ★ same condition
MPZ p.Lys236del Conflicting classifications of pathogenicity ★ same condition
MPZ p.Arg192fs 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-arg67fs (accessed [today's date]).

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