BUB1B p.Pro640=
c.1920G>A · rs755507111 · VCV412524
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.205%, eas)
Conditions
2
Inborn genetic diseases
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 1.8 | GERP -3.1, phastCons 1 |
| Overall | ||
| CADD | 8.016 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.205%
East Asian · 92/44,884 alleles
Filtering AF
0.171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.0083%
134/1,613,982 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.205% | 488 |
| African / African-American | 0.0374% | 2,675 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| South Asian | 0.00329% | 30,362 |
| Admixed American | 0.00167% | 59,994 |
| European (non-Finnish) | 0.000593% | 168,576 |
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
- BUB1B
- Protein
- p.Pro640=
- Coding
- c.1920G>A
- MANE Select
- NM_001211
- dbSNP
- rs755507111
- Type
- single nucleotide variant
- Location
- chr15:40206369 (GRCh38)
- Gene constraint
- LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.62 · 9 PDB
Similar variants
- BUB1B p.Pro640Leu Uncertain significance ★★ ⚠ same residue
- BUB1B p.Arg114Ter Pathogenic ★★ same condition
- BUB1B p.Arg120Ter Pathogenic ★★ same condition
- BUB1B p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
- BUB1B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition
- BUB1B p.Arg67Ter Pathogenic/Likely pathogenic ★★ same condition
- BUB1B p.Gln267Ter Pathogenic ★★ same condition
- BUB1B p.Leu737Ter Pathogenic/Likely pathogenic ★★ same condition
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/bub1b-p-pro640 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown