Is MPZ p.Pro26= (c.78G>A) pathogenic?

MPZ p.Pro26= (c.78G>A) is classified Likely benign in MPZ (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-23). Very rare (popmax 0.00833%, amr); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Pro26= (c.78G>A)?

MPZ p.Pro26= (c.78G>A) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Pro26= (c.78G>A) in the general population?

MPZ p.Pro26= (c.78G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

MPZ p.Pro26=

c.78G>A · rs777790314 · VCV2137786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

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 -9.2	GERP -3.4
Overall
CADD	5.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,034 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00186% 30/1,614,156 alleles · very rare exomes 30/1,461,798 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,007
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	0.00186%	53,638
South Asian	0.0011%	91,076

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.Pro26=
Coding: c.78G>A
MANE Select: NM_000530
dbSNP: rs777790314
Type: single nucleotide variant
Location: chr1:161307414 (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

Charcot-Marie-Tooth disease type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPZ p.Pro26Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MPZ p.Pro26fs Pathogenic ★★ 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

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-pro26 (accessed [today's date]).

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