Is NPHP3 p.Leu1138fs (c.3412_3413del) pathogenic?

NPHP3 p.Leu1138fs (c.34123413del) is classified Likely pathogenic in NPHP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-15). No gnomAD frequency available for this variant; Associated with Enlarged kidney.

What condition is associated with NPHP3 p.Leu1138fs (c.3412_3413del)?

NPHP3 p.Leu1138fs (c.3412_3413del) is associated with Enlarged kidney (ClinVar).

How common is NPHP3 p.Leu1138fs (c.3412_3413del) in the general population?

NPHP3 p.Leu1138fs (c.3412_3413del) is no gnomAD frequency available for this variant (gnomAD).

NPHP3 p.Leu1138fs

c.3412_3413del · rs2107963405 · VCV1328415

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Enlarged kidney

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 24 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.84	GERP 0.11, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NPHP3
Protein: p.Leu1138fs
Coding: c.3412_3413del
MANE Select: NM_153240
dbSNP: rs2107963405
Type: Deletion
Location: chr3:132684711 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.59 · 1 PDB

Full NPHP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

NPHP3 p.Asn761fs Likely pathogenic ★ same condition
NPHP3 c.1888-7_1893del Pathogenic/Likely pathogenic ★★ same type
NPHP3 c.3570+1del Likely pathogenic ★★ same type
NPHP3 p.Arg157fs Pathogenic/Likely pathogenic ★★ same type
NPHP3 p.Glu90_Tyr91insTer Pathogenic/Likely pathogenic ★★ same type
NPHP3 p.His559fs Pathogenic/Likely pathogenic ★★ same type
NPHP3 p.Met491fs Pathogenic/Likely pathogenic ★★ same type
NPHP3 p.Phe1001fs Pathogenic ★★ 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/nphp3-p-leu1138fs (accessed [today's date]).

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