MPZ p.His81=
c.243C>T · rs1571819354 · VCV1148253
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.37e-05%)
Conditions
1
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 7.6 | GERP 0.69, phastCons 1 |
| Overall | ||
| CADD | 11.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.37e-05%
Overall
6.37e-05%
1/1,570,156 alleles · very rare
exomes 1/1,420,004 · genomes 0/150,152 · 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.His81=
- Coding
- c.243C>T
- MANE Select
- NM_000530
- dbSNP
- rs1571819354
- Type
- single nucleotide variant
- Location
- chr1:161306913 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 2 PDB
- Residue 81
- a β-strand; a UniProt-annotated variant site (in cmt1b and cmt2i; severe; reduces intercellular adhesion; does not affect targeting to the cell membrane); a UniProt-annotated variant site (in cmtdid; associated in cis with f-113); the ig-like v-type domain
Similar variants
- MPZ p.His81Arg Pathogenic ★★ ⚠ same residue
- MPZ p.His81Leu Uncertain significance ★★ ⚠ same residue
- MPZ p.His81Tyr Likely pathogenic ★ ⚠ same residue
- MPZ p.His81Gln 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-his81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown