Is MPZ p.Ser8= (c.24C>T) pathogenic?

MPZ p.Ser8= (c.24C>T) is classified Benign/Likely benign in MPZ (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-03). Ultra-rare (popmax 0.0411%, nfe); Associated with Charcot-Marie-Tooth disease.

What condition is associated with MPZ p.Ser8= (c.24C>T)?

MPZ p.Ser8= (c.24C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Ser8= (c.24C>T) in the general population?

MPZ p.Ser8= (c.24C>T) is ultra-rare (popmax 0.0411%, nfe) (gnomAD).

MPZ p.Ser8=

c.24C>T · rs144841836 · VCV462791

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0411%, nfe)

Conditions

Charcot-Marie-Tooth disease

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 2.5	GERP -1.9, phastCons 1
Overall
CADD	9.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0411% European (non-Finnish) · 481/1,169,048 alleles

Filtering AF 0.0381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0369%

Overall 0.033% 524/1,589,372 alleles · ultra-rare exomes 471/1,437,338 · genomes 53/152,034 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0411%	2,430
Finnishnot grpmax-eligible	0.0386%	2,590
Remaining individualsnot grpmax-eligible	0.0178%	5,605
Middle Eastern	0.0166%	6,022
Admixed American	0.0109%	9,147
African / African-American	0.00134%	74,734

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.Ser8=
Coding: c.24C>T
MANE Select: NM_000530
dbSNP: rs144841836
Type: single nucleotide variant
Location: chr1:161309882 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 1

Similar variants

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
MPZ c.68-1G>A Pathogenic/Likely pathogenic ★★ same condition
MPZ c.68-1G>C Pathogenic/Likely pathogenic ★★ same condition
MPZ c.68-2A>C 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-ser8 (accessed [today's date]).

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