NPHP1 p.Cys604fs
c.1811dup · VCV4716456
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
nephronophthisis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (20 of 20) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -3.9 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- NPHP1
- Protein
- p.Cys604fs
- Coding
- c.1811dup
- MANE Select
- NM_001128178
- Type
- Duplication
- Location
- chr2:110124013 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.22 · 2 PDB
Disease context
nephronophthisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Nephronophthisis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Finland)
Similar variants
- NPHP1 p.Cys604Gly Uncertain significance ★ ⚠ same residue
- NPHP1 p.Leu340fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 p.Pro186fs Pathogenic ★★ same condition
- NPHP1 p.Thr461fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 c.144-11dup Benign/Likely benign ★★ same condition
- NPHP1 p.Gln282fs Pathogenic ★ same condition
- NPHP1 p.Leu494fs Pathogenic ★ same condition
- NPHP1 p.Phe617fs 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-cys604fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown