Is DZIP1 p.Val750fs (c.2248dup) pathogenic?

DZIP1 p.Val750fs (c.2248dup) is classified Likely pathogenic in DZIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). Associated with spermatogenic failure 47.

What condition is associated with DZIP1 p.Val750fs (c.2248dup)?

DZIP1 p.Val750fs (c.2248dup) is associated with spermatogenic failure 47 (ClinVar).

DZIP1 p.Val750fs

c.2248dup · VCV4845739

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spermatogenic failure 47

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.3	GERP -0.063, phastCons 1

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

Variant & gene context

Gene: DZIP1
Protein: p.Val750fs
Coding: c.2248dup
MANE Select: NM_198968
Type: Duplication
Location: chr13:95586106 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.55
Residue 750: a UniProt-annotated variant site (in spgf47; decreased protein abundance; changed ciliary basal body organization; loss of sperm flagellum assembly); the 'disordered' region

Full DZIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DZIP1 p.His262Arg Uncertain significance ★★ ⚠ same condition
DZIP1 p.Ser369fs Likely pathogenic ★ same condition
DZIP1 p.Ser24Arg Uncertain significance ★ ⚠ same condition
DZIP1 p.Arg63Gln Pathogenic same condition
DZIP1 p.Tyr230Ter Pathogenic same condition
DZIP1 c.37-5dup 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/dzip1-p-val750fs (accessed [today's date]).

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