NPHP4 p.Pro1055=
c.3165C>G · rs1166080060 · VCV498706
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00453%, eas)
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 0.44 | GERP -3.9, phastCons 0.021 |
| Overall | ||
| CADD | 6.457 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00453%
East Asian · 2/44,128 alleles
Filtering AF
0.000751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000281%
Overall
0.000188%
3/1,597,842 alleles · very rare
exomes 3/1,445,476 · genomes 0/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00453% | 22,064 |
| Admixed American | 0.00172% | 58,064 |
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.Pro1055=
- Coding
- c.3165C>G
- MANE Select
- NM_015102
- dbSNP
- rs1166080060
- Type
- single nucleotide variant
- Location
- chr1:5874537 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
- Residue 1055
- the 'sufficient for basal bodies localization' region
Similar variants
- NPHP4 p.Pro1055Leu Uncertain significance ★ ⚠ same residue
- NPHP4 p.Pro1055Ser 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
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-pro1055 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown