MPZ p.Ile99=
c.297C>A · rs770430402 · VCV1647232
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
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 4.5 | GERP -0.33, phastCons 1 |
| Overall | ||
| CADD | 11.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,868 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000186%
3/1,613,970 alleles · very rare
exomes 3/1,461,850 · genomes 0/152,120 · 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.Ile99=
- Coding
- c.297C>A
- MANE Select
- NM_000530
- dbSNP
- rs770430402
- Type
- single nucleotide variant
- Location
- chr1:161306859 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 2 PDB
- Residue 99
- a β-strand; the ig-like v-type domain; a UniProt-annotated variant site (in cmt1b)
Similar variants
- MPZ p.Ile99Thr Pathogenic ★★ same residue
- MPZ p.Ile99Leu Uncertain significance ★ ⚠ same residue
- MPZ p.Ile99Phe 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
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-ile99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown