PRPF31 p.Arg408=
c.1222C>A · VCV4943867
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000773%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 13.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000773%
European (non-Finnish) · 9/1,164,824 alleles
Filtering AF
0.000364%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000263%
Overall
0.000569%
9/1,581,864 alleles · very rare
exomes 8/1,429,736 · genomes 1/152,128 · joint denominator
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
- PRPF31
- Protein
- p.Arg408=
- Coding
- c.1222C>A
- MANE Select
- NM_015629
- Type
- single nucleotide variant
- Location
- chr19:54129132 (GRCh38)
- Gene constraint
- LOEUF 0.347 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.69 · 30 PDB
Similar variants
- PRPF31 p.Arg408Trp Uncertain significance ★★ ⚠ same residue
- PRPF31 p.Arg408Gln Uncertain significance ★ ⚠ same residue
- PRPF31 c.1073+1G>A Pathogenic ★★ same type
- PRPF31 c.1074-1G>C Likely pathogenic ★★ same type
- PRPF31 c.1074-2A>G Pathogenic ★★ same type
- PRPF31 c.1074-2A>T Pathogenic ★★ same type
- PRPF31 c.1146+2T>C Pathogenic ★★ same type
- PRPF31 c.1146+5G>T 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/prpf31-p-arg408 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown