BUB1 p.Ile986=
c.2958C>T · rs148368189 · VCV1798130
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.62 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.069 | phastCons 0.051 |
| Overall | ||
| CADD | 0.883 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,764 alleles
Filtering AF
0.00625%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00168%
27/1,609,648 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,307 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,173 |
| East Asian | 0.00223% | 44,868 |
| European (non-Finnish) | 0.00119% | 84,010 |
| South Asian | 0.0011% | 90,992 |
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
- BUB1
- Protein
- p.Ile986=
- Coding
- c.2958C>T
- MANE Select
- NM_004336
- dbSNP
- rs148368189
- Type
- single nucleotide variant
- Location
- chr2:110639846 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.91 · 11 PDB
- Residue 986
- the protein kinase domain; an α-helix
Similar variants
- BUB1 p.Ile986Met Uncertain significance ★ ⚠ same residue
- BUB1 p.Ile986Thr Uncertain significance ★ ⚠ same residue
- BUB1 c.1698+1G>T Uncertain significance ★★ same type
- BUB1 p.Ala281Thr Uncertain significance ★★ ⚠ same type
- BUB1 p.Ala283Thr Uncertain significance ★★ ⚠ same type
- BUB1 p.Ala499Val Uncertain significance ★★ ⚠ same type
- BUB1 p.Ala502Ser Uncertain significance ★★ ⚠ same type
- BUB1 p.Ala630Gly 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/bub1-p-ile986 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown