BRSK2 p.His552=
c.1656C>T · rs147039698 · VCV2641340
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.166%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.007 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5 | |
| Overall | ||
| CADD | 8.641 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.166%
European (non-Finnish) · 1,954/1,179,912 alleles
Filtering AF
0.159%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.157%
Overall
0.138%
2,228/1,613,008 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.166% | 604 |
| Remaining individualsnot grpmax-eligible | 0.136% | 735 |
| South Asian | 0.123% | 813 |
| Admixed American | 0.0483% | 2,070 |
| African / African-American | 0.048% | 2,085 |
| East Asian | 0.0134% | 7,477 |
| Finnishnot grpmax-eligible | 0.00951% | 10,517 |
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.His552=
- Coding
- c.1656C>T
- MANE Select
- NM_001256627
- dbSNP
- rs147039698
- Type
- single nucleotide variant
- Location
- chr11:1454596 (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-his552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown