Is MPDZ p.Val1537Phe (c.4609G>T) pathogenic?

MPDZ p.Val1537Phe (c.4609G>T) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely pathogenic (0.7293); Very rare (popmax 0.000173%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPDZ p.Val1537Phe (c.4609G>T)?

MPDZ p.Val1537Phe (c.4609G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPDZ p.Val1537Phe (c.4609G>T) in the general population?

MPDZ p.Val1537Phe (c.4609G>T) is very rare (popmax 0.000173%, nfe) (gnomAD).

What do computational predictors say about MPDZ p.Val1537Phe (c.4609G>T)?

AlphaMissense predicts likely pathogenic (score 0.7293) — an in-silico prediction, not a clinical call.

MPDZ p.Val1537Phe

c.4609G>T · VCV3397583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7293	likely pathogenic
REVEL	0.382	indeterminate
SaProt	LLR -13.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000173% European (non-Finnish) · 2/1,157,952 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000127% 2/1,573,224 alleles · very rare exomes 2/1,420,918 · genomes 0/152,306 · 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.Val1537Phe
Coding: c.4609G>T
MANE Select: NM_001378778
Type: single nucleotide variant
Location: chr9:13126539 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB

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-val1537phe (accessed [today's date]).

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