PRPF8 p.Val728=
c.2184C>G · rs746379730 · VCV1586844
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 0.1 | GERP -1.6, phastCons 0.7 |
| Overall | ||
| CADD | 6.845 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,008 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.000496%
8/1,613,834 alleles · ultra-rare
exomes 8/1,461,670 · genomes 0/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,573 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
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.Val728=
- Coding
- c.2184C>G
- MANE Select
- NM_006445
- dbSNP
- rs746379730
- Type
- single nucleotide variant
- Location
- chr17:1676709 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
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-val728 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown