Is MPZ p.Pro10Leu (c.29C>T) pathogenic?

MPZ p.Pro10Leu (c.29C>T) is classified Uncertain significance in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-23). AlphaMissense: likely benign (0.0883); Very rare (popmax 0.000513%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPZ p.Pro10Leu (c.29C>T)?

MPZ p.Pro10Leu (c.29C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPZ p.Pro10Leu (c.29C>T) in the general population?

MPZ p.Pro10Leu (c.29C>T) is very rare (popmax 0.000513%, nfe) (gnomAD).

What do computational predictors say about MPZ p.Pro10Leu (c.29C>T)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

MPZ p.Pro10Leu

c.29C>T · rs1367546792 · VCV1798634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000513%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.37, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,519 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000513% European (non-Finnish) · 6/1,169,244 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000377% 6/1,589,660 alleles · very rare exomes 4/1,437,660 · genomes 2/152,000 · 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.Pro10Leu
Coding: c.29C>T
MANE Select: NM_000530
dbSNP: rs1367546792
Type: single nucleotide variant
Location: chr1:161309877 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB

Full MPZ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPZ p.Pro10Ala Uncertain significance ★ ⚠ same residue
MPZ c.448+1G>A Pathogenic/Likely pathogenic ★★ same condition
MPZ c.68-1G>A Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Arg98Pro Pathogenic/Likely pathogenic ★★ same condition
MPZ p.Asp224Tyr Pathogenic/Likely pathogenic ★★ same condition
MPZ c.585-6T>C Uncertain significance ★★ same condition
MPZ c.67+4A>G Uncertain significance ★★ same condition
MPZ p.Arg106His Uncertain significance ★★ ⚠ 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-pro10leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown