Is MPDZ p.Pro511Leu (c.1532C>T) pathogenic?

MPDZ p.Pro511Leu (c.1532C>T) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.00588%, afr); Associated with Inborn genetic diseases.

What condition is associated with MPDZ p.Pro511Leu (c.1532C>T)?

MPDZ p.Pro511Leu (c.1532C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPDZ p.Pro511Leu (c.1532C>T) in the general population?

MPDZ p.Pro511Leu (c.1532C>T) is very rare (popmax 0.00588%, afr) (gnomAD).

What do computational predictors say about MPDZ p.Pro511Leu (c.1532C>T)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

MPDZ p.Pro511Leu

c.1532C>T · VCV3397596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.20	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 7.2	GERP 2.4, phastCons 1
Overall
CADD	24.5	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 0.00588% African / African-American · 4/67,992 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00113%

Overall 0.000413% 6/1,453,928 alleles · very rare exomes 4/1,302,012 · genomes 2/151,916 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00588%	16,998
European (non-Finnish)	0.000181%	552,782

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.Pro511Leu
Coding: c.1532C>T
MANE Select: NM_001378778
Type: single nucleotide variant
Location: chr9:13205050 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 511: the pdz 3 domain; a β-strand

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-pro511leu (accessed [today's date]).

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