NPHP1 p.Ser123Asn
c.368G>A · rs781291281 · VCV845883
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0695 | likely benign |
|---|---|---|
| REVEL | 0.039 | moderately benign-leaning |
| SaProt | LLR -7.68 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.38 | GERP -3, phastCons 0.001 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 81 kb · p 0.26 · regional, not allelic |
| Overall | ||
| CADD | 14.39 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,861 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,356 |
| European (non-Finnish)grpmax | 0.00127% | 78,435 |
| South Asian | 0.0011% | 90,998 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- NPHP1
- Protein
- p.Ser123Asn
- Coding
- c.368G>A
- MANE Select
- NM_001128178
- dbSNP
- rs781291281
- Type
- single nucleotide variant
- Location
- chr2:110169960 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.22 · 2 PDB
- Residue 123
- a modified residue (phosphoserine; by ck2); the 'disordered' region
Disease context
nephronophthisis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: nephronophthisis 1Senior-Loken syndrome 1Joubert syndrome with renal defect
For Nephronophthisis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Finland)
Similar variants
- NPHP1 p.Ser123_Glu127del Uncertain significance ★ 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-ser123asn (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown