NPHP1 p.Ser281Ter
c.842C>G · rs2467354598 · VCV2677284
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
Joubert syndrome with renal defect
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 9 of 20 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.27 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.23 | GERP -3.4 |
| Overall | ||
| CADD | 33.0 | 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.Ser281Ter
- Coding
- c.842C>G
- MANE Select
- NM_001128178
- dbSNP
- rs2467354598
- Type
- single nucleotide variant
- Location
- chr2:110163065 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.22 · 2 PDB
Similar variants
- NPHP1 p.Ser281= Likely benign ★ same residue
- NPHP1 c.1083+1G>A Likely pathogenic ★★ same condition
- NPHP1 c.1270-1G>A Pathogenic ★★ same condition
- NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same condition
- 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
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-ser281ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown