NPHP4 p.Arg521=
c.1563G>A · VCV4920418
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.57e-05%, nfe)
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 -4.1 |
| Overall | ||
| CADD | 0.452 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.57e-05%
European (non-Finnish) · 1/1,166,566 alleles
Overall
6.3e-05%
1/1,587,932 alleles · very rare
exomes 1/1,435,582 · genomes 0/152,350 · joint denominator
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.Arg521=
- Coding
- c.1563G>A
- MANE Select
- NM_015102
- Type
- single nucleotide variant
- Location
- chr1:5907163 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
- Residue 521
- the 'disordered' region
Similar variants
- NPHP4 p.Arg521Trp Uncertain significance ★ ⚠ 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
- NPHP4 c.518-2A>G 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-arg521 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown