Is MPDZ p.Thr356Pro (c.1066A>C) pathogenic?

MPDZ p.Thr356Pro (c.1066A>C) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0581); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPDZ p.Thr356Pro (c.1066A>C)?

MPDZ p.Thr356Pro (c.1066A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MPDZ p.Thr356Pro (c.1066A>C) in the general population?

MPDZ p.Thr356Pro (c.1066A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MPDZ p.Thr356Pro (c.1066A>C)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

MPDZ p.Thr356Pro

c.1066A>C · VCV4625188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP -3.8, phastCons 0.013
Overall
CADD	6.099	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,832 alleles

Overall 6.2e-05% 1/1,612,010 alleles · very rare exomes 1/1,459,954 · genomes 0/152,056 · 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.Thr356Pro
Coding: c.1066A>C
MANE Select: NM_001378778
Type: single nucleotide variant
Location: chr9:13219579 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 356: the pdz 1 domain

Full MPDZ 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

Similar variants

MPDZ p.Arg449Ter Pathogenic/Likely pathogenic ★★ same condition
MPDZ c.3254+6T>C Uncertain significance ★★ same condition
MPDZ c.5558-3C>T Uncertain significance ★★ same condition
MPDZ p.Ala104Thr Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala1068Asp Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala10Val Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala1196Gly Uncertain significance ★★ ⚠ same condition
MPDZ p.Ala1227Thr Uncertain significance ★★ ⚠ 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-thr356pro (accessed [today's date]).

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