BUB1B p.Lys250=
c.750G>A · rs1440328650 · VCV952289
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Conditions
1
mosaic variegated aneuploidy syndrome 1
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 3.1 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 14.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,870 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000186%
3/1,613,888 alleles · very rare
exomes 3/1,461,602 · genomes 0/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,435 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,492 |
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
- BUB1B
- Protein
- p.Lys250=
- Coding
- c.750G>A
- MANE Select
- NM_001211
- dbSNP
- rs1440328650
- Type
- single nucleotide variant
- Location
- chr15:40183882 (GRCh38)
- Gene constraint
- LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.62 · 9 PDB
- Residue 250
- a modified residue (n6-acetyllysine; by pcaf)
Similar variants
- BUB1B p.Lys250Asn Uncertain significance ★ ⚠ same residue
- BUB1B p.Lys250Thr Uncertain significance ★ ⚠ same residue
- BUB1B p.Lys250Arg Uncertain significance ★ ⚠ same residue
- BUB1B p.Arg114Ter Pathogenic ★★ same condition
- BUB1B p.Arg120Ter Pathogenic ★★ same condition
- BUB1B p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
- BUB1B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition
- BUB1B p.Arg67Ter Pathogenic/Likely 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/bub1b-p-lys250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown