PRPF8 p.Pro2186=
c.6558G>A · rs551070373 · VCV1623835
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, eas)
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 0.075 | GERP -4.3, phastCons 0.64 |
| Overall | ||
| CADD | 8.658 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
East Asian · 9/44,888 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00167%
27/1,614,102 alleles · ultra-rare
exomes 22/1,461,874 · genomes 5/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.02% | 4,988 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00329% | 30,359 |
| Admixed American | 0.00167% | 60,006 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 0.00102% | 98,334 |
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
- PRPF8
- Protein
- p.Pro2186=
- Coding
- c.6558G>A
- MANE Select
- NM_006445
- dbSNP
- rs551070373
- Type
- single nucleotide variant
- Location
- chr17:1651506 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
- Residue 2186
- the mpn domain
Similar variants
- PRPF8 p.Pro2186Leu Uncertain significance ★ ⚠ same residue
- PRPF8 p.Arg1935His Pathogenic/Likely pathogenic ★★ same type
- PRPF8 p.Arg2310Gly Pathogenic/Likely pathogenic ★★ same type
- PRPF8 p.Arg2310Lys Pathogenic ★★ ⚠ same type
- PRPF8 p.Arg2310Ser Pathogenic ★★ ⚠ same type
- PRPF8 p.Gln2321Ter Pathogenic/Likely pathogenic ★★ same type
- PRPF8 p.His2309Arg Pathogenic ★★ ⚠ same type
- PRPF8 p.His2309Pro Pathogenic/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/prpf8-p-pro2186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown