Is MPDZ p.Leu148Phe (c.442C>T) pathogenic?

MPDZ p.Leu148Phe (c.442C>T) is classified Uncertain significance in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). AlphaMissense: likely pathogenic (0.7698); Absent from gnomAD v4.1.

How common is MPDZ p.Leu148Phe (c.442C>T) in the general population?

MPDZ p.Leu148Phe (c.442C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPDZ p.Leu148Phe (c.442C>T)?

AlphaMissense predicts likely pathogenic (score 0.7698) — an in-silico prediction, not a clinical call.

MPDZ p.Leu148Phe

c.442C>T · rs1959539314 · VCV1480663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7698 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7698	likely pathogenic
REVEL	0.369	indeterminate
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.4, phastCons 1
Overall
CADD	25.6	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

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.Leu148Phe
Coding: c.442C>T
MANE Select: NM_001378778
dbSNP: rs1959539314
Type: single nucleotide variant
Location: chr9:13223662 (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-leu148phe (accessed [today's date]).

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