NPHP3 p.Gly1065fs
c.3192del · VCV4708488
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 22 of 27 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0016% | 62,318 |
| European (non-Finnish)grpmax | 0.00125% | 80,205 |
| South Asian | 0.00114% | 87,380 |
Finnish 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
- NPHP3
- Protein
- p.Gly1065fs
- Coding
- c.3192del
- MANE Select
- NM_153240
- Type
- Deletion
- Location
- chr3:132687160 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.59 · 1 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
- NPHP3 p.Gly1065= Likely benign ★ same residue
- NPHP3 p.Arg157fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP3 p.Glu90_Tyr91insTer Pathogenic/Likely pathogenic ★★ same condition
- NPHP3 p.His559fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP3 p.Phe1001fs Pathogenic ★★ same condition
- NPHP3 p.Thr136fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP3 p.Val363fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP3 c.3697-11_3697-7del Uncertain significance ★★ 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/nphp3-p-gly1065fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown