PRPF4 p.Ala299=
c.897G>A · rs746807835 · VCV1147035
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0209%, sas)
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 -0.028 | GERP -0.95, phastCons 0.91 |
| Overall | ||
| CADD | 11.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0209%
South Asian · 19/91,078 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00297%
48/1,614,022 alleles · ultra-rare
exomes 35/1,461,874 · genomes 13/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0209% | 4,794 |
| African / African-American | 0.016% | 6,243 |
| Finnishnot grpmax-eligible | 0.00156% | 64,030 |
| European (non-Finnish) | 0.00136% | 73,752 |
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.Ala299=
- Coding
- c.897G>A
- MANE Select
- NM_001244926
- dbSNP
- rs746807835
- Type
- single nucleotide variant
- Location
- chr9:113286793 (GRCh38)
- Gene constraint
- LOEUF 0.294 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.33 · 25 PDB
- Residue 299
- a β-strand
Similar variants
- PRPF4 p.Ala299Val Uncertain significance ★★ ⚠ same residue
- PRPF4 p.Ala299Glu Uncertain significance ★ ⚠ same residue
- 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.Arg206Ser Uncertain significance ★★ ⚠ same type
- PRPF4 p.Arg438Trp Uncertain significance ★★ ⚠ same type
- PRPF4 p.Arg439Cys 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-ala299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown