Is MPZ p.Asp118= (c.354C>T) pathogenic?

MPZ p.Asp118= (c.354C>T) is classified Likely benign in MPZ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-28). Very rare (popmax 0.00271%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPZ p.Asp118= (c.354C>T)?

MPZ p.Asp118= (c.354C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Asp118= (c.354C>T) in the general population?

MPZ p.Asp118= (c.354C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

MPZ p.Asp118=

c.354C>T · rs780896055 · VCV531704

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Conditions

Inborn genetic diseases

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 2.9	GERP -1.7, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,180,006 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,613,906 alleles · very rare exomes 33/1,461,866 · genomes 1/152,040 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,875
African / African-American	0.00267%	37,430

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.Asp118=
Coding: c.354C>T
MANE Select: NM_000530
dbSNP: rs780896055
Type: single nucleotide variant
Location: chr1:161306802 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 118: the ig-like v-type domain; a UniProt-annotated variant site (in dss); a UniProt-annotated variant site (in cmt2i)

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

Also linked: Charcot-Marie-Tooth disease type 1

Similar variants

MPZ p.Asp118Asn 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
MPZ c.68-1G>C 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-asp118 (accessed [today's date]).

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