Is MPZ p.Ile30Val (c.88A>G) pathogenic?

MPZ p.Ile30Val (c.88A>G) is classified Conflicting classifications of pathogenicity in MPZ (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-06). AlphaMissense: likely benign (0.3206); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MPZ p.Ile30Val (c.88A>G)?

MPZ p.Ile30Val (c.88A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Ile30Val (c.88A>G) in the general population?

MPZ p.Ile30Val (c.88A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPZ p.Ile30Val (c.88A>G)?

AlphaMissense predicts likely benign (score 0.3206) — an in-silico prediction, not a clinical call.

MPZ p.Ile30Val

c.88A>G · rs1386345719 · VCV1045680

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3206 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3206	likely benign
REVEL	0.47	indeterminate
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 0.68, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	25.4	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.Ile30Val
Coding: c.88A>G
MANE Select: NM_000530
dbSNP: rs1386345719
Type: single nucleotide variant
Location: chr1:161307404 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 30: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 1

Similar variants

MPZ p.Ile30Met Pathogenic ★★ same residue
MPZ p.Ile30Thr Pathogenic/Likely pathogenic ★★ same residue
MPZ p.Ile30Ser Likely pathogenic ★ same residue
MPZ p.Ile30Leu Uncertain significance ★ same residue
MPZ p.Ile30= Likely benign ★ 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-ile30val (accessed [today's date]).

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