Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Common
common (popmax 94.3%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
maturity-onset diabetes of the young type 11
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -2.3, phastCons 1 |
| Overall | ||
| CADD | 9.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
94.3%
East Asian · 42,328/44,868 alleles
Filtering AF
93.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 93.3%
Overall
83.9%
1,354,658/1,614,022 alleles · common
exomes 1,230,750/1,461,874 · genomes 123,908/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 94.3% | 1 |
| Amishnot grpmax-eligible | 89.5% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 88.2% | 1 |
| Admixed American | 86.4% | 1 |
| Remaining individualsnot grpmax-eligible | 84.8% | 1 |
| European (non-Finnish) | 84.6% | 1 |
| Middle Eastern | 83.9% | 1 |
| Finnishnot grpmax-eligible | 81% | 1 |
| South Asian | 77.6% | 1 |
| African / African-American | 73.2% | 1 |
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
- BLK
- Protein
- p.Phe281=
- Coding
- c.843T>C
- MANE Select
- NM_001715
- dbSNP
- rs2306234
- Type
- single nucleotide variant
- Location
- chr8:11556728 (GRCh38)
- Gene constraint
- LOEUF 1.295 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.89
- Residue 281
- the protein kinase domain
Disease context
maturity-onset diabetes of the young type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor MODY (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- BLK p.Arg180His Uncertain significance ★★ ⚠ same condition
- BLK p.Arg295Trp Uncertain significance ★★ same condition
- BLK p.Arg298Gln Uncertain significance ★★ ⚠ same condition
- BLK p.Gln226Pro Uncertain significance ★★ ⚠ same condition
- BLK p.Gly451Ser Uncertain significance ★★ ⚠ same condition
- BLK p.His55Arg Uncertain significance ★★ ⚠ same condition
- BLK p.Ile338Thr Uncertain significance ★★ ⚠ same condition
- BLK p.Leu381Ser Uncertain significance ★★ ⚠ 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/blk-p-phe281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown