NPHP4 p.Gln1050=
c.3150G>A · rs776468806 · VCV288724
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00213%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.99 | GERP -0.38, phastCons 1 |
| Overall | ||
| CADD | 8.872 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00213%
European (non-Finnish) · 25/1,176,150 alleles
Filtering AF
0.00146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00162%
26/1,604,118 alleles · very rare
exomes 25/1,451,918 · genomes 1/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00213% | 47,046 |
| Finnishnot grpmax-eligible | 0.00159% | 62,846 |
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.Gln1050=
- Coding
- c.3150G>A
- MANE Select
- NM_015102
- dbSNP
- rs776468806
- Type
- single nucleotide variant
- Location
- chr1:5874552 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
- Residue 1050
- the 'sufficient for basal bodies localization' region
Similar variants
- NPHP4 p.Gln1050Pro Uncertain significance ★ ⚠ same residue
- NPHP4 p.Gln1050fs Pathogenic/Likely pathogenic ★★ 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-gln1050 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown