Is MPDZ p.Pro819Ser (c.2455C>T) pathogenic?

MPDZ p.Pro819Ser (c.2455C>T) is classified Uncertain significance in MPDZ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-11). AlphaMissense: likely benign (0.0708); Ultra-rare (popmax 0.0104%, amr); Associated with Inborn genetic diseases.

What condition is associated with MPDZ p.Pro819Ser (c.2455C>T)?

MPDZ p.Pro819Ser (c.2455C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPDZ p.Pro819Ser (c.2455C>T) in the general population?

MPDZ p.Pro819Ser (c.2455C>T) is ultra-rare (popmax 0.0104%, amr) (gnomAD).

What do computational predictors say about MPDZ p.Pro819Ser (c.2455C>T)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

MPDZ p.Pro819Ser

c.2455C>T · rs997331523 · VCV1511696

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.15	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 5	GERP 1.5, phastCons 1
Overall
CADD	21.9	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 0.0104% Admixed American · 6/57,530 alleles

Filtering AF 0.00454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00305%

Overall 0.000816% 13/1,592,488 alleles · ultra-rare exomes 10/1,440,326 · genomes 3/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0104%	9,588
Remaining individualsnot grpmax-eligible	0.00973%	10,278
African / African-American	0.00134%	74,470

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.Pro819Ser
Coding: c.2455C>T
MANE Select: NM_001378778
dbSNP: rs997331523
Type: single nucleotide variant
Location: chr9:13186296 (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.Pro819= Likely benign ★ same residue
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

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-pro819ser (accessed [today's date]).

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