NPHP1 c.1761+352del
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0855%, afr)
Conditions
1
nephronophthisis 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +352 | deep intronic (+352 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -2.3 |
| Non-coding constraint | Z 1.24 | 1 kb window · o/e 0.91 · regional · uncalibrated |
| Overall | ||
| CADD | 0.117 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0855%
African / African-American · 62/72,490 alleles
Filtering AF
0.0685%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0623%
Overall
0.0272%
413/1,519,994 alleles · ultra-rare
exomes 341/1,368,734 · genomes 72/151,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0855% | 1,169 |
| Remaining individualsnot grpmax-eligible | 0.0487% | 2,052 |
| Admixed American | 0.0458% | 2,183 |
| South Asian | 0.0352% | 2,845 |
| European (non-Finnish) | 0.0226% | 4,417 |
| East Asian | 0.0172% | 5,802 |
| Middle Eastern | 0.0168% | 5,952 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0106% | 9,475 |
| Finnishnot grpmax-eligible | 0.00452% | 22,104 |
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
- Coding
- c.1761+352del
- MANE Select
- NM_001128178
- Type
- Deletion
- Location
- chr2:110125285 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.22 · 2 PDB
Similar variants
- NPHP1 p.Asn61fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 p.Asp162fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 p.Glu454fs Pathogenic ★★ same condition
- NPHP1 p.Ile517fs Pathogenic ★★ same condition
- NPHP1 p.Ser129fs Pathogenic/Likely pathogenic ★★ same condition
- NPHP1 p.Ser29fs Pathogenic ★★ same condition
- NPHP1 c.1530-4del Likely benign ★★ same condition
- NPHP1 c.1352+1del 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-c-1761-plus-352del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown