Is MPDZ p.Ile1508Met (c.4524A>G) pathogenic?

MPDZ p.Ile1508Met (c.4524A>G) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: ambiguous (0.4795); Ultra-rare (popmax 0.0825%, mid).

How common is MPDZ p.Ile1508Met (c.4524A>G) in the general population?

MPDZ p.Ile1508Met (c.4524A>G) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about MPDZ p.Ile1508Met (c.4524A>G)?

AlphaMissense predicts ambiguous (score 0.4795) — an in-silico prediction, not a clinical call.

MPDZ p.Ile1508Met

c.4524A>G · rs747239643 · VCV1439554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4795	ambiguous
REVEL	0.289	benign-leaning
SaProt	LLR -12.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -3.5, phastCons 0.63
Overall
CADD	17.2	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 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00366% 59/1,613,924 alleles · ultra-rare exomes 54/1,461,618 · genomes 5/152,306 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.0317%	3,159
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00246%	40,684

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.Ile1508Met
Coding: c.4524A>G
MANE Select: NM_001378778
dbSNP: rs747239643
Type: single nucleotide variant
Location: chr9:13126713 (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.Ile1508Arg Uncertain significance ★ ⚠ same residue
MPDZ p.Ile1508Lys 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-ile1508met (accessed [today's date]).

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