Is MPZ p.Asp90= (c.270C>T) pathogenic?

MPZ p.Asp90= (c.270C>T) is classified Likely benign in MPZ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-23). Ultra-rare (popmax 0.0347%, afr); Associated with Charcot-Marie-Tooth disease type 1.

What condition is associated with MPZ p.Asp90= (c.270C>T)?

MPZ p.Asp90= (c.270C>T) is associated with Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Asp90= (c.270C>T) in the general population?

MPZ p.Asp90= (c.270C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

MPZ p.Asp90=

c.270C>T · rs121913584 · VCV872513

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

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 -3.2	GERP -3.4
Overall
CADD	7.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 26/74,832 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00198% 32/1,613,574 alleles · ultra-rare exomes 17/1,461,630 · genomes 15/151,944 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,878
South Asian	0.0011%	91,068
European (non-Finnish)	0.000424%	235,998

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.Asp90=
Coding: c.270C>T
MANE Select: NM_000530
dbSNP: rs121913584
Type: single nucleotide variant
Location: chr1:161306886 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 90: a UniProt-annotated variant site (in cmt1b); the ig-like v-type domain

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.Asp90Glu Pathogenic ★★ ⚠ same residue
MPZ p.Asp90Asn 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
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-asp90 (accessed [today's date]).

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