PRPF6 p.Pro309=
c.927G>A · rs769685223 · VCV1550229
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
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 -6.8 | GERP -3.7 |
| Overall | ||
| CADD | 1.628 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,894 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000558%
9/1,614,022 alleles · very rare
exomes 7/1,461,860 · genomes 2/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,223 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 74,920 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000169% | 590,023 |
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
- PRPF6
- Protein
- p.Pro309=
- Coding
- c.927G>A
- MANE Select
- NM_012469
- dbSNP
- rs769685223
- Type
- single nucleotide variant
- Location
- chr20:63999663 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.07 · 33 PDB
- Residue 309
- an α-helix
Similar variants
- PRPF6 p.Pro309Leu Uncertain significance ★ ⚠ same residue
- PRPF6 c.2028+5G>A Uncertain significance ★★ same type
- PRPF6 c.2205+5G>A Uncertain significance ★★ same type
- PRPF6 c.439-19G>A Uncertain significance ★★ same type
- PRPF6 p.Ala246Val Uncertain significance ★★ ⚠ same type
- PRPF6 p.Ala380Thr Uncertain significance ★★ ⚠ same type
- PRPF6 p.Ala564Thr Uncertain significance ★★ ⚠ same type
- PRPF6 p.Ala65Thr Uncertain significance ★★ ⚠ 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/prpf6-p-pro309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown