NPHP3 c.519+2T>C
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,553,966)
Conditions
1
optic atrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.97 | donor loss, 2 bp away · masked 0 · deltas |
| Pangolin | Δ0.82 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.8, phastCons 1 |
| Non-coding constraint | Z 1.55 | 1 kb window · o/e 0.88 · regional · uncalibrated |
| Overall | ||
| CADD | 28.2 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,553,966). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- NPHP3
- Coding
- c.519+2T>C
- MANE Select
- NM_153240
- Type
- single nucleotide variant
- Location
- chr3:132719703 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.59 · 1 PDB
Similar variants
- NPHP3 c.3570+4A>G Uncertain significance ★★ same condition
- NPHP3 p.Ala1221Val Conflicting classifications of pathogenicity ★ ⚠ same condition
- 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
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-519-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown