Is MPDZ p.Ile1508Arg (c.4523T>G) pathogenic?

MPDZ p.Ile1508Arg (c.4523T>G) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely pathogenic (0.9783); Absent from gnomAD v4.1.

How common is MPDZ p.Ile1508Arg (c.4523T>G) in the general population?

MPDZ p.Ile1508Arg (c.4523T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPDZ p.Ile1508Arg (c.4523T>G)?

AlphaMissense predicts likely pathogenic (score 0.9783) — an in-silico prediction, not a clinical call.

MPDZ p.Ile1508Arg

c.4523T>G · rs1163669825 · VCV1380767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9783	likely pathogenic · top 4% in MPDZ
REVEL	0.472	indeterminate
SaProt	LLR -17.38	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 11	GERP 2.4, phastCons 1
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPDZ
Protein: p.Ile1508Arg
Coding: c.4523T>G
MANE Select: NM_001378778
dbSNP: rs1163669825
Type: single nucleotide variant
Location: chr9:13126714 (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 p.Ile1508Lys Uncertain significance ★ ⚠ same residue
MPDZ p.Ile1508Met Uncertain significance ★ ⚠ same residue
MPDZ p.Ile1508Val Uncertain significance ★ ⚠ same residue
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

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-ile1508arg (accessed [today's date]).

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