PRPF8 p.Ser2017=
c.6051G>A · rs560560988 · VCV1139805
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Conditions
1
inherited retinal dystrophy
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 -20 | GERP -5.5 |
| Overall | ||
| CADD | 0.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,896 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000743%
12/1,614,030 alleles · very rare
exomes 10/1,461,888 · genomes 2/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,965 |
| Admixed American | 0.00333% | 29,999 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00134% | 74,890 |
| European (non-Finnish) | 0.000424% | 236,009 |
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.Ser2017=
- Coding
- c.6051G>A
- MANE Select
- NM_006445
- dbSNP
- rs560560988
- Type
- single nucleotide variant
- Location
- chr17:1653953 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
- Residue 2017
- an α-helix; the 'involved in interaction with pre-mrna 5' splice site' region; the 'rnase h homology domain' region
Similar variants
- PRPF8 p.Ser2017Leu Uncertain significance ★★ ⚠ same residue
- PRPF8 p.Ser2017Trp Uncertain significance ★ ⚠ same residue
- PRPF8 p.Arg1935His Pathogenic/Likely pathogenic ★★ same condition
- PRPF8 p.Arg2310Gly Pathogenic/Likely pathogenic ★★ same condition
- PRPF8 p.Gln2321Ter Pathogenic/Likely pathogenic ★★ same condition
- PRPF8 p.His2313Pro Likely pathogenic ★★ ⚠ same condition
- PRPF8 p.Pro2301Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PRPF8 p.Thr1931Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
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-ser2017 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown