Is MPZ p.Asp128= (c.384C>T) pathogenic?

MPZ p.Asp128= (c.384C>T) is classified Likely benign in MPZ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-11). Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with MPZ p.Asp128= (c.384C>T)?

MPZ p.Asp128= (c.384C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1 (ClinVar).

How common is MPZ p.Asp128= (c.384C>T) in the general population?

MPZ p.Asp128= (c.384C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

MPZ p.Asp128=

c.384C>T · rs772611598 · VCV531702

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.035	GERP -3.7, phastCons 0.076
Overall
CADD	12.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00328% 53/1,613,888 alleles · very rare exomes 45/1,461,884 · genomes 8/152,004 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0437%	2,286
East Asiangrpmax	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.008%	12,495
African / African-American	0.00668%	14,965
South Asian	0.00659%	15,181
European (non-Finnish)	0.000424%	236,005

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp128=
Coding: c.384C>T
MANE Select: NM_000530
dbSNP: rs772611598
Type: single nucleotide variant
Location: chr1:161306772 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI 0.11 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 2 PDB
Residue 128: a β-strand; the ig-like v-type domain; a UniProt-annotated variant site (in cmt1b); a UniProt-annotated variant site (in dss; associated in cis with thr-114 and his-116 in one patient)

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.Asp128Asn Likely pathogenic ★ ⚠ same residue
MPZ p.Asp128His Uncertain significance ★ ⚠ same residue
MPZ p.Asp128Tyr Uncertain significance ★ ⚠ same residue
MPZ p.Asp128delinsGluTer Pathogenic ★ same residue
MPZ p.Asp128Glu Uncertain significance ⚠ same residue
MPZ p.Asp128Gly Uncertain significance ⚠ same residue
MPZ c.235-1G>T Pathogenic/Likely pathogenic ★★ same condition
MPZ c.448+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-asp128 (accessed [today's date]).

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