BSCL2 p.Pro25Leu
c.74C>T · VCV4847945
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0109%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.165 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP 0.21, phastCons 0.015 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic |
| Overall | ||
| CADD | 16.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0109%
African / African-American · 8/73,122 alleles
Filtering AF
0.00539%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00389%
Overall
0.000837%
13/1,553,614 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0109% | 9,140 |
| South Asian | 0.00594% | 16,845 |
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
- BSCL2
- Protein
- p.Pro25Leu
- Coding
- c.74C>T
- MANE Select
- NM_001122955
- Type
- single nucleotide variant
- Location
- chr11:62707122 (GRCh38)
- Gene constraint
- LOEUF 0.869 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.09 · 1 PDB
Similar variants
- GNG3 p.Ile25Thr Uncertain significance ★ ⚠ same residue
- BSCL2 c.1006-2A>C Likely pathogenic ★★ same type
- BSCL2 c.1006-2A>G Pathogenic/Likely pathogenic ★★ same type
- BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same type
- BSCL2 c.631-1G>C Pathogenic/Likely pathogenic ★★ same type
- BSCL2 c.766-2A>G Pathogenic ★★ same type
- BSCL2 p.Ala276Pro Pathogenic ★★ same type
- BSCL2 p.Arg202Ter 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/bscl2-p-pro25leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown