Is NPHP4 p.Leu101fs (c.302del) pathogenic?

NPHP4 p.Leu101fs (c.302del) is classified Likely pathogenic in NPHP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-31). Associated with NPHP4-related disorder.

What condition is associated with NPHP4 p.Leu101fs (c.302del)?

NPHP4 p.Leu101fs (c.302del) is associated with NPHP4-related disorder (ClinVar).

NPHP4 p.Leu101fs

c.302del · VCV4924780

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 4 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.4	GERP -2.7, phastCons 0.16

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

Variant & gene context

Gene: NPHP4
Protein: p.Leu101fs
Coding: c.302del
MANE Select: NM_015102
Type: Deletion
Location: chr1:5969237 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.44

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.Ala279fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Glu978fs Pathogenic ★★ same condition
NPHP4 p.Lys424fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Tyr1137fs Pathogenic/Likely pathogenic ★★ same condition
NPHP4 p.Val1091fs Pathogenic ★★ same condition
NPHP4 c.1503+1del Likely pathogenic ★ same condition
NPHP4 p.Pro593_Ser594insTer Likely pathogenic ★ same condition
NPHP4 p.Ser463fs Likely 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-leu101fs (accessed [today's date]).

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