PRPF40A p.Ser646=
c.1938A>G · rs113359796 · VCV711345
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.14%, afr)
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 -1.3 | GERP -5, phastCons 0.001 |
| Overall | ||
| CADD | 5.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.14%
African / African-American · 1,600/74,914 alleles
Filtering AF
2.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.01%
Overall
0.12%
1,930/1,610,484 alleles · low-frequency
exomes 1,026/1,458,166 · genomes 904/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.14% | 47 |
| Remaining individualsnot grpmax-eligible | 0.213% | 469 |
| Admixed American | 0.195% | 512 |
| Middle Eastern | 0.165% | 605 |
| South Asian | 0.0066% | 15,162 |
| European (non-Finnish) | 0.00544% | 18,391 |
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
- PRPF40A
- Protein
- p.Ser646=
- Coding
- c.1938A>G
- MANE Select
- NM_001365597
- dbSNP
- rs113359796
- Type
- single nucleotide variant
- Location
- chr2:152664205 (GRCh38)
- Gene constraint
- LOEUF 0.44 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.14 · 12 PDB
- Residue 646
- the ff 4 domain
Similar variants
- PRPF40A p.Ala150Val Uncertain significance ★ same type
- PRPF40A p.Ala225Thr Uncertain significance ★ same type
- PRPF40A p.Ala297Gly Uncertain significance ★ same type
- PRPF40A p.Ala298Val Uncertain significance ★ same type
- PRPF40A p.Ala306Gly Uncertain significance ★ same type
- PRPF40A p.Ala355Val Uncertain significance ★ same type
- PRPF40A p.Ala445Val Uncertain significance ★ same type
- PRPF40A p.Ala548Thr 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/prpf40a-p-ser646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown