BRSK2 p.Pro456=
c.1368G>A · rs373710927 · VCV3053156
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.116%, afr)
Conditions
1
Inborn genetic diseases
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 -3.7 | |
| Overall | ||
| CADD | 6.634 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.116%
African / African-American · 87/74,846 alleles
Filtering AF
0.0965%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0892%
Overall
0.0206%
331/1,609,242 alleles · rare
exomes 277/1,456,926 · genomes 54/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.116% | 860 |
| European (non-Finnish) | 0.0182% | 5,482 |
| South Asian | 0.0154% | 6,477 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,897 |
| Admixed American | 0.00505% | 19,795 |
| Finnishnot grpmax-eligible | 0.00481% | 20,802 |
| East Asian | 0.00448% | 22,300 |
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.Pro456=
- Coding
- c.1368G>A
- MANE Select
- NM_001256627
- dbSNP
- rs373710927
- Type
- single nucleotide variant
- Location
- chr11:1450667 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.46
- Residue 456
- the 'disordered' region
Similar variants
- BRSK2 p.Pro456Leu Uncertain significance ★ ⚠ same residue
- BRSK2 p.Arg65Gln Uncertain significance ★★ ⚠ same condition
- BRSK2 p.Asp7Asn Uncertain significance ★★ ⚠ same condition
- BRSK2 p.Gly391Ser Likely benign ★★ ⚠ same condition
- BRSK2 p.Gly578Ala Benign/Likely benign ★★ same condition
- BRSK2 p.Pro502Leu Likely benign ★★ same condition
- BRSK2 c.1226+1G>A Likely pathogenic ★ same condition
- BRSK2 c.978-1G>C Pathogenic ★ same condition
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-pro456 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown