Is MPZ p.Ser44Pro (c.130T>C) pathogenic?

MPZ p.Ser44Pro (c.130T>C) is classified Likely pathogenic in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-01). AlphaMissense: likely pathogenic (0.9923); Absent from gnomAD v4.1; Associated with motor neuron disorder.

What condition is associated with MPZ p.Ser44Pro (c.130T>C)?

MPZ p.Ser44Pro (c.130T>C) is associated with motor neuron disorder (ClinVar).

How common is MPZ p.Ser44Pro (c.130T>C) in the general population?

MPZ p.Ser44Pro (c.130T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPZ p.Ser44Pro (c.130T>C)?

AlphaMissense predicts likely pathogenic (score 0.9923) — an in-silico prediction, not a clinical call.

MPZ p.Ser44Pro

c.130T>C · rs2102260097 · VCV1328480

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

motor neuron disorder

Computational evidence

Protein change
AlphaMissense	0.9923	likely pathogenic ✓ concordant with ClinVar · top 9% in MPZ
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -16.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.69, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPZ
Protein: p.Ser44Pro
Coding: c.130T>C
MANE Select: NM_000530
dbSNP: rs2102260097
Type: single nucleotide variant
Location: chr1:161307362 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 44: a UniProt-annotated variant site (in cmt2i and cmt1b); the ig-like v-type domain

Full MPZ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

motor neuron disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPZ p.Ser44Phe Pathogenic ★★ same residue
MPZ p.Ser44Cys Uncertain significance ⚠ same residue
MPZ p.Ser44fs Pathogenic/Likely pathogenic ★★ same residue
MPZ p.Ser44_Thr47del Pathogenic ★ same residue
MPZ c.235-1G>T Pathogenic/Likely pathogenic ★★ same type
MPZ c.448+1G>A Pathogenic/Likely pathogenic ★★ same type
MPZ c.448+1G>T Likely pathogenic ★★ same type
MPZ c.448+2T>G Likely pathogenic ★★ same type

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-ser44pro (accessed [today's date]).

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