NPHP4 p.Asp3=
c.9C>T · rs745503891 · VCV290374
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0428%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.7 | GERP -1.5, phastCons 0.99 |
| Overall | ||
| CADD | 1.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0428%
South Asian · 39/91,028 alleles
Filtering AF
0.0322%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0285%
Overall
0.00248%
40/1,613,730 alleles · ultra-rare
exomes 40/1,461,414 · genomes 0/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0428% | 2,334 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
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
- NPHP4
- Protein
- p.Asp3=
- Coding
- c.9C>T
- MANE Select
- NM_015102
- dbSNP
- rs745503891
- Type
- single nucleotide variant
- Location
- chr1:5986281 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
- Residue 3
- a UniProt-annotated variant site (in slsn4)
Similar variants
- NPHP4 p.Asp3Asn Uncertain significance ★★ ⚠ same residue
- NPHP4 p.Asp3Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
- NPHP4 c.2304+1G>A Pathogenic ★★ same type
- NPHP4 c.2611+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHP4 c.2611+1G>C Pathogenic ★★ same type
- NPHP4 c.3644+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHP4 c.3644+1G>T Pathogenic/Likely pathogenic ★★ same type
- NPHP4 c.517+1G>A 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/nphp4-p-asp3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown