Is NPHP1 p.Ser349fs (c.1044_1053del) pathogenic?

NPHP1 p.Ser349fs (c.10441053del) is classified Likely pathogenic in NPHP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). Associated with nephronophthisis 1.

What condition is associated with NPHP1 p.Ser349fs (c.1044_1053del)?

NPHP1 p.Ser349fs (c.1044_1053del) is associated with nephronophthisis 1, Senior-Loken syndrome 1, Joubert syndrome with renal defect (ClinVar).

NPHP1 p.Ser349fs

c.1044_1053del · VCV3584253

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

nephronophthisis 1

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 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.7, phastCons 0.97

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

Variant & gene context

Gene: NPHP1
Protein: p.Ser349fs
Coding: c.1044_1053del
MANE Select: NM_001128178
Type: Deletion
Location: chr2:110160157 (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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Senior-Loken syndrome 1 Joubert syndrome with renal defect

Similar variants

NPHP1 c.141_143+40del Likely pathogenic ★★ same condition
NPHP1 p.Asn61fs Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Asp162fs Pathogenic/Likely pathogenic ★★ same condition
NPHP1 p.Glu454fs Pathogenic ★★ same condition
NPHP1 p.Ile517fs Pathogenic ★★ same condition
NPHP1 p.Lys185fs Pathogenic ★★ same condition
NPHP1 p.Lys377fs Pathogenic ★★ same condition
NPHP1 p.Ser129fs Pathogenic/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/nphp1-p-ser349fs (accessed [today's date]).

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