Is MPDZ p.Val455fs (c.1364_1365del) pathogenic?

MPDZ p.Val455fs (c.13641365del) is classified Pathogenic in MPDZ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Very rare (popmax 0.00167%, amr).

How common is MPDZ p.Val455fs (c.1364_1365del) in the general population?

MPDZ p.Val455fs (c.1364_1365del) is very rare (popmax 0.00167%, amr) (gnomAD).

MPDZ p.Val455fs

c.1364_1365del · rs1564026963 · VCV1458966

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 5.1	GERP 0.81, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,904 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,612,480 alleles · very rare exomes 6/1,461,066 · genomes 0/151,414 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,904
European (non-Finnish)	0.000424%	235,894

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.Val455fs
Coding: c.1364_1365del
MANE Select: NM_001378778
dbSNP: rs1564026963
Type: Microsatellite
Location: chr9:13206025 (GRCh38)
Structure: AlphaFold pLDDT 72.11 · 3 PDB
Residue 455: the pdz 2 domain

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

Similar variants

MPDZ p.Leu1274fs Pathogenic/Likely pathogenic ★★ same type
MPDZ p.Glu515del Uncertain significance ★★ same type
MPDZ p.Glu1286fs Pathogenic ★ same type
MPDZ p.Leu1773fs Likely pathogenic ★ same type
MPDZ p.Trp1672fs Pathogenic ★ same type
MPDZ c.5467-13_5467-11del Uncertain significance ★ same type
MPDZ c.748-6_748-3del Uncertain significance ★ same type
MPDZ p.65ATS[1] Uncertain significance ★ 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-val455fs (accessed [today's date]).

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