BUB1 p.Ala106=
c.318G>C · rs370559107 · VCV1728648
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.108%, amr)
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 · C>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -13 | |
| Overall | ||
| CADD | 0.022 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.108%
Admixed American · 65/59,964 alleles
Filtering AF
0.0872%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0796%
Overall
0.0365%
589/1,613,956 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.108% | 923 |
| European (non-Finnish) | 0.0431% | 2,323 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,680 |
| African / African-American | 0.00667% | 14,983 |
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.Ala106=
- Coding
- c.318G>C
- MANE Select
- NM_004336
- dbSNP
- rs370559107
- Type
- single nucleotide variant
- Location
- chr2:110672765 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.91 · 11 PDB
- Residue 106
- the bub1 n-terminal domain; the 'necessary for kinetochore localization' region; the 'necessary for interaction with knl1' region; an α-helix
Similar variants
- BUB1 p.Ala106Val 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-ala106 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown