BRSK2 p.Pro440=
c.1320C>T · VCV3350081
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0499%, mid)
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 5.7 | phastCons 1 |
| Overall | ||
| CADD | 15.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0499%
Middle Eastern · 3/6,012 alleles
Filtering AF
0.0135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00859%
Overall
0.00989%
158/1,597,046 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0499% | 2,004 |
| African / African-American | 0.0176% | 5,686 |
| Remaining individualsnot grpmax-eligible | 0.0146% | 6,852 |
| European (non-Finnish) | 0.0107% | 9,319 |
| South Asian | 0.0056% | 17,856 |
| East Asian | 0.00227% | 44,028 |
| Admixed American | 0.00179% | 55,832 |
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.Pro440=
- Coding
- c.1320C>T
- MANE Select
- NM_001256627
- Type
- single nucleotide variant
- Location
- chr11:1450619 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.46
- Residue 440
- the 'disordered' region
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-pro440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown