Is NPHP4 p.Lys1332fs (c.3993dup) pathogenic?

NPHP4 p.Lys1332fs (c.3993dup) is classified Likely pathogenic in NPHP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-25). Associated with NPHP4-related disorder.

What condition is associated with NPHP4 p.Lys1332fs (c.3993dup)?

NPHP4 p.Lys1332fs (c.3993dup) is associated with NPHP4-related disorder (ClinVar).

NPHP4 p.Lys1332fs

c.3993dup · VCV4910620

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

NPHP4-related disorder

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 28 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: NPHP4
Protein: p.Lys1332fs
Coding: c.3993dup
MANE Select: NM_015102
Type: Duplication
Location: chr1:5864340 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44
Residue 1332: the 'sufficient for basal bodies localization' region

Full NPHP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NPHP4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NPHP4 p.Arg934fs Likely pathogenic ★ same condition
NPHP4 p.Pro143fs Likely pathogenic ★ same condition
NPHP4 p.Val816fs Likely pathogenic ★ same condition
NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 c.517+1G>A Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Ala279fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Arg59Ter Pathogenic ★★ same condition

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/nphp4-p-lys1332fs (accessed [today's date]).

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