Is NPHP1 p.Leu526del (c.1573TTG[1]) pathogenic?

NPHP1 p.Leu526del (c.1573TTG[1]) is classified Uncertain significance in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). Associated with nephronophthisis.

What condition is associated with NPHP1 p.Leu526del (c.1573TTG[1])?

NPHP1 p.Leu526del (c.1573TTG[1]) is associated with nephronophthisis (ClinVar).

How is Nephronophthisis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NPHP1 p.Leu526del

c.1573TTG[1] · VCV4777873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

nephronophthisis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.69	GERP -3.7

Variant & gene context

Gene: NPHP1
Protein: p.Leu526del
Coding: c.1573TTG[1]
MANE Select: NM_001128178
Type: Microsatellite
Location: chr2:110131743 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.22 · 2 PDB

Full NPHP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

NPHP1 p.Leu526Phe Uncertain significance ★ ⚠ same residue
NPHP1 p.Leu526Trp Uncertain significance ★ same residue
NPHP1 p.Leu526= Likely benign ★ same residue
NPHP1 c.522+5_522+8del Uncertain significance ★★ same condition
NPHP1 c.771+77_771+78del Pathogenic ★ same condition
NPHP1 p.Glu141_Glu142del Conflicting classifications of pathogenicity ★ same condition
NPHP1 p.Glu215dup Conflicting classifications of pathogenicity ★ same condition
NPHP1 c.1270-1G>A 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/nphp1-p-leu526del (accessed [today's date]).

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