PRPF8 p.Arg35=
c.103C>A · rs144810783 · VCV1011432
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.67 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.24 | gain · loss 0.18 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 22.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
African / African-American · 10/74,786 alleles
Filtering AF
0.00724%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00551%
Overall
0.00105%
17/1,613,566 alleles · ultra-rare
exomes 11/1,461,716 · genomes 6/151,850 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0134% | 7,479 |
| Admixed American | 0.00834% | 11,991 |
| European (non-Finnish) | 0.000169% | 589,995 |
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.Arg35=
- Coding
- c.103C>A
- MANE Select
- NM_006445
- dbSNP
- rs144810783
- Type
- single nucleotide variant
- Location
- chr17:1683699 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
- Residue 35
- an α-helix
Similar variants
- PRPF8 p.Arg35Leu 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-arg35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown