BUB1 p.Pro66=
c.198A>G · rs891883323 · VCV1783921
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00684%, afr)
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 2.9 | phastCons 1 |
| Overall | ||
| CADD | 11.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00684%
African / African-American · 5/73,134 alleles
Filtering AF
0.0026%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00165%
Overall
0.000455%
7/1,539,370 alleles · very rare
exomes 3/1,387,122 · genomes 4/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00684% | 14,627 |
| East Asian | 0.00225% | 44,410 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 60,052 |
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.Pro66=
- Coding
- c.198A>G
- MANE Select
- NM_004336
- dbSNP
- rs891883323
- Type
- single nucleotide variant
- Location
- chr2:110674113 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.91 · 11 PDB
- Residue 66
- the bub1 n-terminal domain; the 'necessary for kinetochore localization' region; an α-helix
Similar variants
- BUB1 p.Pro66Arg 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
- BUB1 p.Ala705Thr 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-pro66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown