Is MPDZ p.Val321fs (c.960del) pathogenic?

MPDZ p.Val321fs (c.960del) is classified Pathogenic in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-02). Very rare (popmax 6.2e-05%).

How common is MPDZ p.Val321fs (c.960del) in the general population?

MPDZ p.Val321fs (c.960del) is very rare (popmax 6.2e-05%) (gnomAD).

MPDZ p.Val321fs

c.960del · rs1958831021 · VCV1447384

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,612,668 alleles · very rare exomes 0/1,460,672 · genomes 1/151,996 · 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.Val321fs
Coding: c.960del
MANE Select: NM_001378778
dbSNP: rs1958831021
Type: Deletion
Location: chr9:13219685 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 321: the pdz 1 domain

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

Similar variants

MPDZ p.Val321= Likely benign ★ same residue
MPDZ p.Gln1490fs Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Gly1682fs Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Phe138fs Pathogenic ★★ same type
MPDZ p.Ser1966fs Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Gly1492del Uncertain significance ★★ same type
MPDZ c.5601+2_5601+3del Likely pathogenic ★ same type
MPDZ p.Asp647fs 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-val321fs (accessed [today's date]).

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