MPZ p.Leu14Pro
c.41T>C · VCV4278866
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
AlphaMissense
likely benign
0.1214 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Charcot-Marie-Tooth disease type 1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1214 | likely benign |
|---|---|---|
| REVEL | 0.825 | moderately pathogenic-leaning |
| SaProt | LLR -11.05 | damaging |
| ⇒ REVEL and SaProt call this damaging; AlphaMissense does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.69 | unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | 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.Leu14Pro
- Coding
- c.41T>C
- MANE Select
- NM_000530
- Type
- single nucleotide variant
- Location
- chr1:161309865 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 2 PDB
Similar variants
- MPZ p.Leu14= 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
- 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-leu14pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown