Is MPZ p.Trp101fs (c.301dup) pathogenic?

MPZ p.Trp101fs (c.301dup) is classified Pathogenic in MPZ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-06). Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPZ p.Trp101fs (c.301dup)?

MPZ p.Trp101fs (c.301dup) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Trp101fs (c.301dup) in the general population?

MPZ p.Trp101fs (c.301dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

MPZ p.Trp101fs

c.301dup · rs2526238723 · VCV1798896

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Inborn genetic diseases

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 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,002 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,000 alleles · very rare exomes 4/1,461,858 · genomes 0/152,142 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MPZ
Protein: p.Trp101fs
Coding: c.301dup
MANE Select: NM_000530
dbSNP: rs2526238723
Type: Duplication
Location: chr1:161306854 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 101: a β-strand; the ig-like v-type domain; a UniProt-annotated variant site (in cmt1b)

Full MPZ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 1

Similar variants

MPZ p.Trp101Arg Likely pathogenic ★★ same residue
MPZ p.Trp101Ter Pathogenic ★★ same residue
MPZ p.Glu91fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Thr216fs Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Asp128delinsGluTer Pathogenic ★ same condition
MPZ p.Asp61fs Pathogenic ★ same condition
MPZ p.Lys138fs Pathogenic ★ same condition
MPZ p.Lys201fs 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-trp101fs (accessed [today's date]).

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