Is MPDZ p.Pro788Ser (c.2362C>T) pathogenic?

MPDZ p.Pro788Ser (c.2362C>T) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-29). AlphaMissense: likely benign (0.3205); Absent from gnomAD v4.1; Associated with hydrocephalus, nonsyndromic, autosomal recessive 2.

What condition is associated with MPDZ p.Pro788Ser (c.2362C>T)?

MPDZ p.Pro788Ser (c.2362C>T) is associated with hydrocephalus, nonsyndromic, autosomal recessive 2 (ClinVar).

How common is MPDZ p.Pro788Ser (c.2362C>T) in the general population?

MPDZ p.Pro788Ser (c.2362C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPDZ p.Pro788Ser (c.2362C>T)?

AlphaMissense predicts likely benign (score 0.3205) — an in-silico prediction, not a clinical call.

MPDZ p.Pro788Ser

c.2362C>T · VCV4884592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3205 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hydrocephalus, nonsyndromic, autosomal recessive 2

Computational evidence

Protein change
AlphaMissense	0.3205	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.3, phastCons 1
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPDZ
Protein: p.Pro788Ser
Coding: c.2362C>T
MANE Select: NM_001378778
Type: single nucleotide variant
Location: chr9:13188786 (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.Pro788= Uncertain significance ★★ same residue
MPDZ p.Pro788Thr Benign/Likely benign ★★ same residue
MPDZ c.1474+2T>C Likely pathogenic ★★ same condition
MPDZ c.3359+1G>A Likely pathogenic ★★ same condition
MPDZ c.3360-2A>G Pathogenic/Likely pathogenic ★★ same condition
MPDZ c.4003+1G>A Pathogenic/Likely pathogenic ★★ same condition
MPDZ p.Arg1071Ter Pathogenic ★★ same condition
MPDZ p.Arg1170Ter 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-pro788ser (accessed [today's date]).

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