Is MPDZ p.Ser1296Arg (c.3886A>C) pathogenic?

MPDZ p.Ser1296Arg (c.3886A>C) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1514); Very rare (popmax 0.00398%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MPDZ p.Ser1296Arg (c.3886A>C)?

MPDZ p.Ser1296Arg (c.3886A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MPDZ p.Ser1296Arg (c.3886A>C) in the general population?

MPDZ p.Ser1296Arg (c.3886A>C) is very rare (popmax 0.00398%, nfe) (gnomAD).

What do computational predictors say about MPDZ p.Ser1296Arg (c.3886A>C)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

MPDZ p.Ser1296Arg

c.3886A>C · VCV3912595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.23	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 -0.25	GERP -4.5
Overall
CADD	13.04	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 0.00398% European (non-Finnish) · 47/1,179,778 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00304% 49/1,613,372 alleles · very rare exomes 48/1,461,548 · genomes 1/151,824 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,102
Remaining individualsnot grpmax-eligible	0.0032%	31,226

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.Ser1296Arg
Coding: c.3886A>C
MANE Select: NM_001378778
Type: single nucleotide variant
Location: chr9:13140104 (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.Ser1296Thr Uncertain significance ★ ⚠ same residue
MPDZ p.Ser1296Asn Uncertain significance ★ ⚠ 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

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-ser1296arg (accessed [today's date]).

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