BRSK2 p.Pro277=
c.831C>T · rs201409224 · VCV3025076
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.122%, amr)
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 -20 | |
| Overall | ||
| CADD | 0.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.122%
Admixed American · 73/59,810 alleles
Filtering AF
0.0995%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0913%
Overall
0.075%
1,207/1,610,162 alleles · rare
exomes 1,110/1,457,798 · genomes 97/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.122% | 819 |
| European (non-Finnish) | 0.09% | 1,111 |
| Remaining individualsnot grpmax-eligible | 0.0674% | 1,483 |
| African / African-American | 0.0267% | 3,750 |
| Middle Eastern | 0.0165% | 6,048 |
| South Asian | 0.00992% | 10,076 |
| East Asian | 0.00223% | 44,790 |
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.Pro277=
- Coding
- c.831C>T
- MANE Select
- NM_001256627
- dbSNP
- rs201409224
- Type
- single nucleotide variant
- Location
- chr11:1445312 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.46
Similar variants
- 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
- BRSK2 c.1288-6A>G Likely benign ★★ 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-pro277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown