BUB1B p.Ser435=
c.1305T>C · rs1295708566 · VCV2585916
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,066 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,613,912 alleles · very rare
exomes 3/1,461,610 · genomes 0/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,066 |
| European (non-Finnish) | 0.00017% | 589,929 |
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.Ser435=
- Coding
- c.1305T>C
- MANE Select
- NM_001211
- dbSNP
- rs1295708566
- Type
- single nucleotide variant
- Location
- chr15:40199631 (GRCh38)
- Gene constraint
- LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.62 · 9 PDB
- Residue 435
- a modified residue (phosphoserine)
Similar variants
- BUB1B p.Ser435Asn Uncertain significance ★ ⚠ same residue
- BUB1B c.35+4G>T Uncertain significance ★★ same condition
- BUB1B p.Ala1017Thr Uncertain significance ★★ ⚠ same condition
- BUB1B p.Ala1046Pro Uncertain significance ★★ ⚠ same condition
- BUB1B p.Ala108Thr Uncertain significance ★★ ⚠ same condition
- BUB1B p.Ala171Pro Uncertain significance ★★ ⚠ same condition
- BUB1B p.Ala173Thr Uncertain significance ★★ ⚠ same condition
- BUB1B p.Ala183Thr Uncertain significance ★★ ⚠ 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-ser435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown