Is MPDZ p.Ser879fs (c.2633dup) pathogenic?

MPDZ p.Ser879fs (c.2633dup) is classified Pathogenic in MPDZ (ClinVar, Single submitter, 1 submitter). Very rare (popmax 6.22e-05%); Associated with hydrocephalus, nonsyndromic, autosomal recessive 2.

What condition is associated with MPDZ p.Ser879fs (c.2633dup)?

MPDZ p.Ser879fs (c.2633dup) is associated with hydrocephalus, nonsyndromic, autosomal recessive 2 (ClinVar).

How common is MPDZ p.Ser879fs (c.2633dup) in the general population?

MPDZ p.Ser879fs (c.2633dup) is very rare (popmax 6.22e-05%) (gnomAD).

MPDZ p.Ser879fs

c.2633dup · VCV3383154

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

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 -2.2	GERP -4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,606,800 alleles · very rare exomes 1/1,454,798 · genomes 0/152,002 · joint denominator

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.Ser879fs
Coding: c.2633dup
MANE Select: NM_001378778
Type: Duplication
Location: chr9:13183433 (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.Leu400fs Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Leu448fs Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Ser963fs Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Ser879Leu Uncertain significance ★★ ⚠ same residue
MPDZ p.Leu501fs Pathogenic ★ same condition
MPDZ p.Ser879= Likely benign ★ same residue
MPDZ p.Tyr2005fs Likely pathogenic same condition
MPDZ c.1474+2T>C 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/mpdz-p-ser879fs (accessed [today's date]).

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