Is MPZ p.Val165fs (c.491dup) pathogenic?

MPZ p.Val165fs (c.491dup) is classified Pathogenic in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-18). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Val165fs (c.491dup)?

MPZ p.Val165fs (c.491dup) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Val165fs (c.491dup) in the general population?

MPZ p.Val165fs (c.491dup) is no gnomAD frequency available for this variant (gnomAD).

MPZ p.Val165fs

c.491dup · rs1558153783 · VCV949390

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -0.3	GERP -3.1, phastCons 0.003

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.Val165fs
Coding: c.491dup
MANE Select: NM_000530
dbSNP: rs1558153783
Type: Duplication
Location: chr1:161306421 (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.Glu91fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Thr216fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Trp101fs Pathogenic ★★ same condition
MPZ p.Asp128delinsGluTer Pathogenic ★ same condition
MPZ p.Lys138fs Pathogenic ★ same condition
MPZ p.Ser78fs Pathogenic ★ same condition
MPZ p.Tyr88Ter Pathogenic ★ same condition
MPZ c.235-9_267dup Uncertain significance ★ 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-val165fs (accessed [today's date]).

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