BRSK2 p.Pro465=
c.1395G>A · rs370281113 · VCV2641336
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.079 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.56 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -6 | |
| Overall | ||
| CADD | 4.081 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Admixed American · 10/59,192 alleles
Filtering AF
0.00929%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00873%
Overall
0.0104%
168/1,608,750 alleles · ultra-rare
exomes 150/1,456,438 · genomes 18/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0169% | 5,919 |
| South Asian | 0.0143% | 6,970 |
| East Asian | 0.0112% | 8,924 |
| European (non-Finnish) | 0.0109% | 9,207 |
| Remaining individualsnot grpmax-eligible | 0.00803% | 12,454 |
| African / African-American | 0.00802% | 12,471 |
| Finnishnot grpmax-eligible | 0.0016% | 62,362 |
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
- BRSK2
- Protein
- p.Pro465=
- Coding
- c.1395G>A
- MANE Select
- NM_001256627
- dbSNP
- rs370281113
- Type
- single nucleotide variant
- Location
- chr11:1450694 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.46
- Residue 465
- the 'disordered' region
Similar variants
- BRSK2 p.Pro465Leu Uncertain significance ★ ⚠ same residue
- BRSK2 p.Arg313Ter Pathogenic/Likely pathogenic ★★ same type
- BRSK2 p.Gly28Arg Likely pathogenic ★★ same type
- BRSK2 p.Ala68Thr Uncertain significance ★★ ⚠ same type
- BRSK2 p.Arg313Gln Uncertain significance ★★ same type
- BRSK2 p.Arg65Gln Uncertain significance ★★ ⚠ same type
- BRSK2 p.Asp7Asn Uncertain significance ★★ ⚠ same type
- BRSK2 p.Leu70Pro 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/brsk2-p-pro465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown