NPHP3 c.*651del
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 41.8%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.051 | GERP -0.51, phastCons 0.044 |
| Overall | ||
| CADD | 0.497 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
41.8%
East Asian · 1,140/2,728 alleles
Filtering AF
39.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 39%
Overall
8.93%
9,437/105,728 alleles · common
exomes 1/74 · genomes 9,436/105,654 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 41.8% | 2 |
| South Asian | 14.7% | 7 |
| African / African-American | 11.6% | 9 |
| Middle Eastern | 10.1% | 10 |
| Amishnot grpmax-eligible | 9.52% | 10 |
| Remaining individualsnot grpmax-eligible | 9.16% | 11 |
| European (non-Finnish) | 6.48% | 15 |
| Admixed American | 6.47% | 15 |
| Ashkenazi Jewishnot grpmax-eligible | 6.34% | 16 |
| Finnishnot grpmax-eligible | 4.31% | 23 |
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
- NPHP3
- Coding
- c.*651del
- MANE Select
- NM_153240
- dbSNP
- rs886058000
- Type
- Deletion
- Location
- chr3:132681259 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.59 · 1 PDB
Similar variants
- NPHP3 c.1888-7_1893del Pathogenic/Likely pathogenic ★★ same type
- NPHP3 c.3570+1del Likely pathogenic ★★ same type
- NPHP3 p.Arg157fs Pathogenic/Likely pathogenic ★★ same type
- NPHP3 p.Glu90_Tyr91insTer Pathogenic/Likely pathogenic ★★ same type
- NPHP3 p.His559fs Pathogenic/Likely pathogenic ★★ same type
- NPHP3 p.Met491fs Pathogenic/Likely pathogenic ★★ same type
- NPHP3 p.Phe1001fs Pathogenic ★★ same type
- NPHP3 p.Thr136fs 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/nphp3-c-star-651del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown