BRSK2 p.Ala477=
c.1431G>A · rs368914488 · VCV3051167
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0332%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.112 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.3 | |
| Overall | ||
| CADD | 1.761 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0332%
Middle Eastern · 2/6,020 alleles
Filtering AF
0.0172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0164%
Overall
0.0167%
267/1,601,042 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0332% | 3,010 |
| Remaining individualsnot grpmax-eligible | 0.021% | 4,761 |
| European (non-Finnish) | 0.0193% | 5,181 |
| South Asian | 0.0145% | 6,884 |
| Admixed American | 0.0106% | 9,411 |
| African / African-American | 0.00404% | 24,767 |
| Finnishnot grpmax-eligible | 0.00321% | 31,166 |
| East Asian | 0.00225% | 44,450 |
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.Ala477=
- Coding
- c.1431G>A
- MANE Select
- NM_001256627
- dbSNP
- rs368914488
- Type
- single nucleotide variant
- Location
- chr11:1450730 (GRCh38)
- Gene constraint
- LOEUF 0.361 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.46
Similar variants
- BRSK2 p.Ala477Val 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-ala477 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown