NPHP1 p.Cys604=
c.1812C>T · VCV4956431
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.22 | gain · loss 0.19 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -6 | GERP -3.9 |
| Overall | ||
| CADD | 3.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00142%
23/1,614,042 alleles · ultra-rare
exomes 21/1,461,778 · genomes 2/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| Finnishnot grpmax-eligible | 0.00312% | 32,005 |
| East Asian | 0.00223% | 44,882 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| African / African-American | 0.00133% | 75,044 |
| European (non-Finnish) | 0.00119% | 84,280 |
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.Cys604=
- Coding
- c.1812C>T
- MANE Select
- NM_001128178
- Type
- single nucleotide variant
- Location
- chr2:110124013 (GRCh38)
- Gene constraint
- LOEUF 0.92 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.22 · 2 PDB
Similar variants
- NPHP1 p.Cys604Gly Uncertain significance ★ ⚠ same residue
- NPHP1 p.Cys604fs Pathogenic ★ same residue
- NPHP1 c.1083+1G>A Likely pathogenic ★★ same type
- NPHP1 c.1270-1G>A Pathogenic ★★ same type
- NPHP1 c.1270-2A>G Pathogenic/Likely pathogenic ★★ same type
- NPHP1 c.143+1G>C Likely pathogenic ★★ same type
- NPHP1 c.144-1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHP1 c.1716+1G>T 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/nphp1-p-cys604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown