PRPF6 p.Leu331=
c.993T>C · VCV4945915
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.64 | GERP -3.7, phastCons 0.037 |
| Overall | ||
| CADD | 4.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,878 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00062%
10/1,614,146 alleles · ultra-rare
exomes 9/1,461,868 · genomes 1/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,976 |
| South Asian | 0.00439% | 22,770 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
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.Leu331=
- Coding
- c.993T>C
- MANE Select
- NM_012469
- Type
- single nucleotide variant
- Location
- chr20:63999729 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.07 · 33 PDB
- Residue 331
- an α-helix
Similar variants
- 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
- PRPF6 p.Ala675Thr 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-leu331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown