PRPF4 p.Ser415=
c.1245C>T · rs1389388359 · VCV1088879
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 0.15 | GERP 1.6, phastCons 0.94 |
| Overall | ||
| CADD | 8.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,018 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00031%
5/1,614,070 alleles · very rare
exomes 5/1,461,794 · genomes 0/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,006 |
| European (non-Finnish) | 0.000169% | 589,977 |
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
- PRPF4
- Protein
- p.Ser415=
- Coding
- c.1245C>T
- MANE Select
- NM_001244926
- dbSNP
- rs1389388359
- Type
- single nucleotide variant
- Location
- chr9:113290799 (GRCh38)
- Gene constraint
- LOEUF 0.294 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.33 · 25 PDB
- Residue 415
- a β-strand
Similar variants
- PRPF4 p.Pro314Leu Likely pathogenic ★★ same type
- PRPF4 c.654+4A>T Uncertain significance ★★ same type
- PRPF4 p.Ala195Thr Uncertain significance ★★ ⚠ same type
- PRPF4 p.Ala299Val Uncertain significance ★★ ⚠ same type
- PRPF4 p.Arg206Ser Uncertain significance ★★ ⚠ same type
- PRPF4 p.Arg438Trp Uncertain significance ★★ ⚠ same type
- PRPF4 p.Arg439Cys Uncertain significance ★★ ⚠ same type
- PRPF4 p.Asn241Ser Uncertain significance ★★ ⚠ 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/prpf4-p-ser415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown