PRPF8 p.Ala2000=
c.6000A>G · rs745954222 · VCV1097868
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
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 -4.4 | GERP -5.5 |
| Overall | ||
| CADD | 3.702 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,082 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.00254%
41/1,614,070 alleles · ultra-rare
exomes 34/1,461,892 · genomes 7/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,027 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| African / African-American | 0.00267% | 37,457 |
| European (non-Finnish) | 0.00254% | 39,335 |
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.Ala2000=
- Coding
- c.6000A>G
- MANE Select
- NM_006445
- dbSNP
- rs745954222
- Type
- single nucleotide variant
- Location
- chr17:1654004 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
- Residue 2000
- an α-helix; the 'involved in interaction with pre-mrna 5' splice site' region; the 'rnase h homology domain' region
Similar variants
- 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
- PRPF8 p.His2313Pro 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-ala2000 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown