MPZ p.Val58=
c.174C>T · rs753575261 · VCV917383
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00768%, sas)
Conditions
1
Charcot-Marie-Tooth disease
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 4.3 | GERP -0.33, phastCons 1 |
| Overall | ||
| CADD | 10.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00768%
South Asian · 7/91,088 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.000496%
8/1,614,280 alleles · very rare
exomes 8/1,461,878 · genomes 0/152,402 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00768% | 13,013 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
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.Val58=
- Coding
- c.174C>T
- MANE Select
- NM_000530
- dbSNP
- rs753575261
- Type
- single nucleotide variant
- Location
- chr1:161307318 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 2 PDB
- Residue 58
- a UniProt-annotated variant site (in cmt1b; moderate); the ig-like v-type domain
Similar variants
- MPZ p.Val58Phe Uncertain significance ★★ ⚠ same residue
- MPZ p.Val58Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
- MPZ c.448+2T>G Likely pathogenic ★★ same condition
- MPZ c.584+2T>G Pathogenic ★★ same condition
- MPZ p.Arg227Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- MPZ p.Arg98His Pathogenic/Likely pathogenic ★★ same condition
- MPZ p.Arg98Pro Pathogenic/Likely pathogenic ★★ same condition
- MPZ p.Asp224Tyr 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-val58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown