Is MPZ p.Ile79Val (c.235A>G) pathogenic?

MPZ p.Ile79Val (c.235A>G) is classified Uncertain significance in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely benign (0.1934); Very rare (popmax 8.49e-05%, nfe); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Ile79Val (c.235A>G)?

MPZ p.Ile79Val (c.235A>G) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Ile79Val (c.235A>G) in the general population?

MPZ p.Ile79Val (c.235A>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about MPZ p.Ile79Val (c.235A>G)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

MPZ p.Ile79Val

c.235A>G · rs2526239163 · VCV1718119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 1

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.51, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,498 alleles

Overall 6.22e-05% 1/1,606,784 alleles · very rare exomes 1/1,458,208 · genomes 0/148,576 · 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.Ile79Val
Coding: c.235A>G
MANE Select: NM_000530
dbSNP: rs2526239163
Type: single nucleotide variant
Location: chr1:161306921 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 79: a β-strand; 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.Ile79Thr 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
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

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-ile79val (accessed [today's date]).

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