BUB1 p.Leu136=
c.408G>C · rs1690453050 · VCV2565782
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0027%, 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 -0.46 | phastCons 0.074 |
| Overall | ||
| CADD | 3.342 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0027%
African / African-American · 2/74,054 alleles
Filtering AF
0.000448%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000168%
Overall
0.000139%
2/1,439,972 alleles · very rare
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.Leu136=
- Coding
- c.408G>C
- MANE Select
- NM_004336
- dbSNP
- rs1690453050
- Type
- single nucleotide variant
- Location
- chr2:110672675 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.91 · 11 PDB
- Residue 136
- the bub1 n-terminal domain; the 'necessary for kinetochore localization' region; an α-helix
Similar variants
- BUB1 p.Leu136Pro 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-leu136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown