NPHP1 p.Gln289Ter
c.865C>T · rs2104548702 · VCV1679279
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
nephronophthisis 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 10 of 20 |
| Splicing | ||
| SpliceAI | Δ0.46 | acceptor gain · deltas |
| Pangolin | Δ0.41 | loss · gain 0.31 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 45.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- NPHP1
- Protein
- p.Gln289Ter
- Coding
- c.865C>T
- MANE Select
- NM_001128178
- dbSNP
- rs2104548702
- Type
- single nucleotide variant
- Location
- chr2:110161692 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.22 · 2 PDB
Similar variants
- NPHP1 p.Gln289= Conflicting classifications of pathogenicity ★ same residue
- NPHP1 p.Gln289Pro Uncertain significance ★ ⚠ same residue
- NPHP1 c.143+1G>C Likely pathogenic ★★ same condition
- NPHP1 c.144-1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 c.1716+1G>T Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 c.329+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 c.522+1G>A Likely pathogenic ★★ same condition
- NPHP1 c.729-2A>G 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-gln289ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown