PRPF8 p.Val338=
c.1014A>G · rs781046979 · VCV1965304
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00398%, nfe)
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 -5.2 | GERP -4.7 |
| Overall | ||
| CADD | 1.392 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00398%
European (non-Finnish) · 47/1,179,942 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00275%
Overall
0.00304%
49/1,614,004 alleles · very rare
exomes 49/1,461,802 · genomes 0/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00398% | 25,105 |
| East Asian | 0.00223% | 44,882 |
| African / African-American | 0.00133% | 75,002 |
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.Val338=
- Coding
- c.1014A>G
- MANE Select
- NM_006445
- dbSNP
- rs781046979
- Type
- single nucleotide variant
- Location
- chr17:1680810 (GRCh38)
- Gene constraint
- LOEUF 0.26 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.20 · 100 PDB
Similar variants
- PRPF8 p.Val338Ala 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-val338 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown