NPHP3 c.1985+4C>T
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00447%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.28 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -3.1 |
| Non-coding constraint | Z 0.02 | 1 kb window · o/e 1.00 · regional · uncalibrated |
| Overall | ||
| CADD | 3.089 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00447%
East Asian · 2/44,778 alleles
Filtering AF
0.00074%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000277%
Overall
0.000816%
13/1,593,788 alleles · very rare
exomes 13/1,441,582 · genomes 0/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00447% | 22,389 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,906 |
| South Asian | 0.0011% | 90,652 |
| European (non-Finnish) | 0.000774% | 129,180 |
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
- Coding
- c.1985+4C>T
- MANE Select
- NM_153240
- dbSNP
- rs752335903
- Type
- single nucleotide variant
- Location
- chr3:132699349 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.59 · 1 PDB
Similar variants
- NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHP3 c.3201+1G>T Likely pathogenic ★★ same type
- NPHP3 c.393+1G>C Likely pathogenic ★★ same type
- NPHP3 c.520-1G>T Pathogenic ★★ same type
- NPHP3 c.823+1G>T Likely pathogenic ★★ same type
- NPHP3 c.958-2A>G Pathogenic ★★ same type
- NPHP3 p.Arg1125Ter Pathogenic ★★ same type
- NPHP3 p.Arg1259Ter Pathogenic/Likely pathogenic ★★ same type
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-c-1985-plus-4c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown