Is MPZ p.Thr34= (c.102C>T) pathogenic?

MPZ p.Thr34= (c.102C>T) is classified Likely benign in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). Very rare (popmax 0.00445%, eas); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Thr34= (c.102C>T)?

MPZ p.Thr34= (c.102C>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Thr34= (c.102C>T) in the general population?

MPZ p.Thr34= (c.102C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

MPZ p.Thr34=

c.102C>T · rs749600926 · VCV775970

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP -3.7, phastCons 0.01
Overall
CADD	9.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,894 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000743% 12/1,614,256 alleles · very rare exomes 12/1,461,888 · genomes 0/152,368 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,447
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000424%	236,009

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.Thr34=
Coding: c.102C>T
MANE Select: NM_000530
dbSNP: rs749600926
Type: single nucleotide variant
Location: chr1:161307390 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 34: a UniProt-annotated variant site (in cmt1b); 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 type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPZ p.Thr34Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MPZ p.Thr34Ser Uncertain significance ★ ⚠ same residue
MPZ p.Thr34_Asp35del Pathogenic ★ same residue
MPZ c.235-1G>T Pathogenic/Likely pathogenic ★★ same condition
MPZ c.448+1G>A Pathogenic/Likely pathogenic ★★ same condition
MPZ c.448+1G>T Likely pathogenic ★★ same condition
MPZ c.448+2T>G Likely pathogenic ★★ same condition
MPZ c.584+2T>G 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-thr34 (accessed [today's date]).

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