MPZ p.Pro217=
c.651A>G · rs2526233350 · VCV3068891
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
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 -4.8 | GERP -3.1 |
| Overall | ||
| CADD | 4.233 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,882 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,942 alleles · very rare
exomes 4/1,461,748 · genomes 0/152,194 · 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.Pro217=
- Coding
- c.651A>G
- MANE Select
- NM_000530
- dbSNP
- rs2526233350
- Type
- single nucleotide variant
- Location
- chr1:161305972 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 2 PDB
- Residue 217
- a UniProt-annotated variant site (in chn2)
Similar variants
- MPZ p.Pro217Ala Uncertain significance ★ same residue
- MPZ p.Pro217Ser Uncertain significance ⚠ same residue
- MPZ c.235-1G>T Pathogenic/Likely pathogenic ★★ same type
- MPZ c.448+1G>A Pathogenic/Likely pathogenic ★★ same type
- MPZ c.448+1G>T Likely pathogenic ★★ same type
- MPZ c.448+2T>G Likely pathogenic ★★ same type
- MPZ c.584+2T>G Pathogenic ★★ same type
- MPZ c.68-1G>A Pathogenic/Likely pathogenic ★★ same type
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-pro217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown