PRPF8 p.Val445=
c.1335C>G · rs1912780033 · VCV1162166
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, 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 1.6 | GERP -0.59, phastCons 1 |
| Overall | ||
| CADD | 7.141 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,888 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00105%
17/1,613,858 alleles · ultra-rare
exomes 17/1,461,636 · genomes 0/152,222 · 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
- PRPF8
- Protein
- p.Val445=
- Coding
- c.1335C>G
- MANE Select
- NM_006445
- dbSNP
- rs1912780033
- Type
- single nucleotide variant
- Location
- chr17:1679365 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
- Residue 445
- an α-helix
Similar variants
- PRPF8 p.Val445Ile 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
- PRPF8 p.Ala1704Thr Uncertain significance ★★ ⚠ 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-val445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown