Is MPZ p.Ser54= (c.162C>A) pathogenic?

MPZ p.Ser54= (c.162C>A) is classified Likely benign in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). Very rare (popmax 0.00305%, nfe); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Ser54= (c.162C>A)?

MPZ p.Ser54= (c.162C>A) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Ser54= (c.162C>A) in the general population?

MPZ p.Ser54= (c.162C>A) is very rare (popmax 0.00305%, nfe) (gnomAD).

MPZ p.Ser54=

c.162C>A · rs373911573 · VCV934786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00305%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.85, phastCons 1
Overall
CADD	15.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00305% European (non-Finnish) · 36/1,180,068 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00223% 36/1,614,168 alleles · very rare exomes 35/1,461,886 · genomes 1/152,282 · 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.Ser54=
Coding: c.162C>A
MANE Select: NM_000530
dbSNP: rs373911573
Type: single nucleotide variant
Location: chr1:161307330 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 54: a UniProt-annotated variant site (in cmt1b; affects targeting to the cell membrane; reduces intercellular adhesion); 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.Ser54Ala Uncertain significance ★ ⚠ same residue
MPZ p.Ser54Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MPZ p.Ser54Phe Uncertain significance ★ ⚠ same residue
MPZ p.Ser54Pro Uncertain significance ⚠ 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

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-ser54 (accessed [today's date]).

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