Is MPZ p.Ser7Ter (c.20C>G) pathogenic?

MPZ p.Ser7Ter (c.20C>G) is classified Pathogenic in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-29). Very rare (popmax 8.55e-05%, nfe); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Ser7Ter (c.20C>G)?

MPZ p.Ser7Ter (c.20C>G) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Ser7Ter (c.20C>G) in the general population?

MPZ p.Ser7Ter (c.20C>G) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

MPZ p.Ser7Ter

c.20C>G · rs1558155838 · VCV940939

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 0.36, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,169,236 alleles

Overall 6.29e-05% 1/1,589,746 alleles · very rare exomes 1/1,437,610 · genomes 0/152,136 · 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.Ser7Ter
Coding: c.20C>G
MANE Select: NM_000530
dbSNP: rs1558155838
Type: single nucleotide variant
Location: chr1:161309886 (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 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-ser7ter (accessed [today's date]).

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