Is MPZ p.Asp75fs (c.223del) pathogenic?

MPZ p.Asp75fs (c.223del) is classified Uncertain significance in MPZ (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease.

What condition is associated with MPZ p.Asp75fs (c.223del)?

MPZ p.Asp75fs (c.223del) is associated with Charcot-Marie-Tooth disease (ClinVar).

How common is MPZ p.Asp75fs (c.223del) in the general population?

MPZ p.Asp75fs (c.223del) is no gnomAD frequency available for this variant (gnomAD).

MPZ p.Asp75fs

c.223del · rs1571819824 · VCV637786

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease

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 7.9	GERP 0.68, 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.Asp75fs
Coding: c.223del
MANE Select: NM_000530
dbSNP: rs1571819824
Type: Deletion
Location: chr1:161307269 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 75: a UniProt-annotated variant site (in cmt2j and cmt2i); 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPZ p.Asp104fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Ile162fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Leu144fs 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
MPZ p.Asp75Tyr Uncertain significance ★★ ⚠ same residue
MPZ p.Asp75Val Pathogenic ★ ⚠ same residue

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-asp75fs (accessed [today's date]).

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