BUB1 p.Leu82=
c.246C>T · rs751808971 · VCV2451224
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00665%, sas)
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 0.009 | |
| Overall | ||
| CADD | 4.833 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00665%
South Asian · 6/90,190 alleles
Filtering AF
0.00289%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00197%
Overall
0.00048%
7/1,456,892 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00665% | 15,032 |
| European (non-Finnish) | 8.49e-05% | 1,178,238 |
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.Leu82=
- Coding
- c.246C>T
- MANE Select
- NM_004336
- dbSNP
- rs751808971
- Type
- single nucleotide variant
- Location
- chr2:110672837 (GRCh38)
- Gene constraint
- LOEUF 0.727 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.91 · 11 PDB
- Residue 82
- the bub1 n-terminal domain; the 'necessary for kinetochore localization' region; an α-helix
Similar variants
- BUB1 p.Leu82Phe 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-leu82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown