NPHP3 c.1628+116A>T
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.23%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +116 | deep intronic (+116 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.18 | GERP -2.8 |
| Non-coding constraint | Z 0.47 | 1 kb window · o/e 0.97 · regional · uncalibrated |
| Overall | ||
| CADD | 0.618 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.23%
African / African-American · 1,263/56,678 alleles
Filtering AF
2.13%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.09%
Overall
0.192%
1,368/711,528 alleles · low-frequency
exomes 398/559,170 · genomes 970/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.23% | 45 |
| Remaining individualsnot grpmax-eligible | 0.14% | 715 |
| Admixed American | 0.0907% | 1,102 |
| Middle Eastern | 0.0495% | 2,022 |
| South Asian | 0.0138% | 7,262 |
| European (non-Finnish) | 0.00179% | 55,945 |
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.1628+116A>T
- MANE Select
- NM_153240
- dbSNP
- rs77904309
- Type
- single nucleotide variant
- Location
- chr3:132701314 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.59 · 1 PDB
Similar variants
- NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same type
- NPHP3 c.3201+1G>T Likely pathogenic ★★ same type
- NPHP3 c.393+1G>C Likely pathogenic ★★ same type
- NPHP3 c.520-1G>T Pathogenic ★★ same type
- NPHP3 c.823+1G>T Likely pathogenic ★★ same type
- NPHP3 c.958-2A>G Pathogenic ★★ same type
- NPHP3 p.Arg1125Ter Pathogenic ★★ same type
- NPHP3 p.Arg1259Ter 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-1628-plus-116a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown