Is MPDZ p.Ser763Arg (c.2289T>G) pathogenic?

MPDZ p.Ser763Arg (c.2289T>G) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). AlphaMissense: likely pathogenic (0.706); Very rare (popmax 0.00223%, eas).

How common is MPDZ p.Ser763Arg (c.2289T>G) in the general population?

MPDZ p.Ser763Arg (c.2289T>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MPDZ p.Ser763Arg (c.2289T>G)?

AlphaMissense predicts likely pathogenic (score 0.706) — an in-silico prediction, not a clinical call.

MPDZ p.Ser763Arg

c.2289T>G · rs2134852227 · VCV1389972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.706	likely pathogenic
REVEL	0.276	benign-leaning
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 1.1, phastCons 0.99
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,850 alleles

Overall 6.2e-05% 1/1,613,562 alleles · very rare exomes 1/1,461,344 · genomes 0/152,218 · 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.Ser763Arg
Coding: c.2289T>G
MANE Select: NM_001378778
dbSNP: rs2134852227
Type: single nucleotide variant
Location: chr9:13188859 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB

Full MPDZ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPDZ c.1087-1G>A Pathogenic/Likely pathogenic ★★ same type
MPDZ c.1474+2T>C Likely pathogenic ★★ same type
MPDZ c.3359+1G>A Likely pathogenic ★★ same type
MPDZ c.3360-2A>G Pathogenic/Likely pathogenic ★★ same type
MPDZ c.4003+1G>A Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Arg1034Ter Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Arg1071Ter Pathogenic ★★ same type
MPDZ p.Arg1170Ter Pathogenic ★★ same type

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-ser763arg (accessed [today's date]).

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