Is MPZ p.Pro205fs (c.613_616del) pathogenic?

MPZ p.Pro205fs (c.613616del) is classified Pathogenic in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Pro205fs (c.613_616del)?

MPZ p.Pro205fs (c.613_616del) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

MPZ p.Pro205fs

c.613_616del · VCV3648193

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 29 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.53	GERP -2.7

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

Variant & gene context

Gene: MPZ
Protein: p.Pro205fs
Coding: c.613_616del
MANE Select: NM_000530
Type: Deletion
Location: chr1:161306137 (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.Pro205Leu 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-pro205fs (accessed [today's date]).

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