Is MPZ p.Ser78= (c.234G>T) pathogenic?

MPZ p.Ser78= (c.234G>T) is classified Uncertain significance in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). Very rare (popmax 0.005%, amr); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Ser78= (c.234G>T)?

MPZ p.Ser78= (c.234G>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Ser78= (c.234G>T) in the general population?

MPZ p.Ser78= (c.234G>T) is very rare (popmax 0.005%, amr) (gnomAD).

MPZ p.Ser78=

c.234G>T · rs368149365 · VCV2964034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 0.013	GERP -2.6, phastCons 0.78
Overall
CADD	17.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,028 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,204 alleles · very rare exomes 1/1,461,842 · genomes 2/152,362 · 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.Ser78=
Coding: c.234G>T
MANE Select: NM_000530
dbSNP: rs368149365
Type: single nucleotide variant
Location: chr1:161307258 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 78: a β-strand; a UniProt-annotated variant site (in cmt1b; severe); 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.Ser78Leu Pathogenic/Likely pathogenic ★★ same residue
MPZ p.Ser78Trp Pathogenic/Likely pathogenic ★★ same residue
MPZ p.Ser78Pro Uncertain significance ★ ⚠ same residue
MPZ p.Ser78fs Pathogenic ★ same residue
MPZ p.Ser78Ter 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

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-ser78 (accessed [today's date]).

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