PRPF3 p.Pro319=
c.957T>C · rs199721048 · VCV198519
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 10.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
European (non-Finnish) · 143/1,179,978 alleles
Filtering AF
0.0105%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00981%
Overall
0.0096%
155/1,613,952 alleles · ultra-rare
exomes 142/1,461,858 · genomes 13/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0121% | 8,252 |
| South Asian | 0.00878% | 11,385 |
| Admixed American | 0.00333% | 29,992 |
| African / African-American | 0.00267% | 37,455 |
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
- PRPF3
- Protein
- p.Pro319=
- Coding
- c.957T>C
- MANE Select
- NM_004698
- dbSNP
- rs199721048
- Type
- single nucleotide variant
- Location
- chr1:150335163 (GRCh38)
- Gene constraint
- LOEUF 0.087 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.75 · 30 PDB
Similar variants
- PRPF3 p.Arg449Gly Pathogenic/Likely pathogenic ★★ same type
- PRPF3 p.His499Pro Pathogenic ★★ same type
- PRPF3 p.Pro493Ser Pathogenic ★★ same type
- PRPF3 p.Thr494Met Pathogenic ★★ same type
- PRPF3 p.Ala489Pro Uncertain significance ★★ ⚠ same type
- PRPF3 p.Arg641Gln Uncertain significance ★★ ⚠ same type
- PRPF3 p.Asp43Gly Uncertain significance ★★ ⚠ same type
- PRPF3 p.Gln445Arg 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/prpf3-p-pro319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown