Is MPDZ p.Phe138fs (c.414del) pathogenic?

MPDZ p.Phe138fs (c.414del) is classified Pathogenic in MPDZ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-28). Very rare (popmax 0.00134%, afr); Associated with hydrocephalus, nonsyndromic, autosomal recessive 2.

What condition is associated with MPDZ p.Phe138fs (c.414del)?

MPDZ p.Phe138fs (c.414del) is associated with hydrocephalus, nonsyndromic, autosomal recessive 2 (ClinVar).

How common is MPDZ p.Phe138fs (c.414del) in the general population?

MPDZ p.Phe138fs (c.414del) is very rare (popmax 0.00134%, afr) (gnomAD).

MPDZ p.Phe138fs

c.414del · rs1267168609 · VCV1323286

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hydrocephalus, nonsyndromic, autosomal recessive 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,570 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00056% 9/1,607,146 alleles · very rare exomes 8/1,455,242 · genomes 1/151,904 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,570
European (non-Finnish)	0.00068%	147,083

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: MPDZ
Protein: p.Phe138fs
Coding: c.414del
MANE Select: NM_001378778
dbSNP: rs1267168609
Type: Deletion
Location: chr9:13223690 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB

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

Disease context

hydrocephalus, nonsyndromic, autosomal recessive 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPDZ p.Gln1490fs Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Gly1682fs Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Ser1966fs Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Gly1638fs Likely pathogenic ★ same condition
MPDZ p.Ser1498fs Likely pathogenic ★ same condition
LNX1 p.Lys138Arg Uncertain significance ★ ⚠ same residue
MPDZ p.Leu33fs Conflicting classifications of pathogenicity ★ same condition
MPDZ p.Phe138Ser Uncertain significance ★ ⚠ same residue

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/mpdz-p-phe138fs (accessed [today's date]).

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