PRPF3 p.Ala623=
c.1869T>C · rs781962153 · VCV740428
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 4.2 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 13.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00474%
Overall
0.00508%
82/1,613,802 alleles · ultra-rare
exomes 75/1,461,624 · genomes 7/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| Admixed American | 0.00667% | 14,995 |
| European (non-Finnish) | 0.00636% | 15,732 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
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
- PRPF3
- Protein
- p.Ala623=
- Coding
- c.1869T>C
- MANE Select
- NM_004698
- dbSNP
- rs781962153
- Type
- single nucleotide variant
- Location
- chr1:150349182 (GRCh38)
- Gene constraint
- LOEUF 0.087 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.75 · 30 PDB
Similar variants
- PRPF3 p.Arg449Gly Pathogenic/Likely pathogenic ★★ same type
- PRPF3 p.His499Pro Pathogenic ★★ same type
- PRPF3 p.Pro493Ser Pathogenic ★★ same type
- PRPF3 p.Thr494Met Pathogenic ★★ same type
- PRPF3 p.Ala489Pro Uncertain significance ★★ ⚠ same type
- PRPF3 p.Arg641Gln Uncertain significance ★★ ⚠ same type
- PRPF3 p.Asp43Gly Uncertain significance ★★ ⚠ same type
- PRPF3 p.Gln445Arg 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/prpf3-p-ala623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown