Is BUB1B p.Lys94= (c.282G>A) pathogenic?

BUB1B p.Lys94= (c.282G>A) is classified Benign/Likely benign in BUB1B (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 14.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with colorectal cancer.

What condition is associated with BUB1B p.Lys94= (c.282G>A)?

BUB1B p.Lys94= (c.282G>A) is associated with colorectal cancer, premature chromatid separation trait, mosaic variegated aneuploidy syndrome 1 (ClinVar).

BUB1B p.Lys94=

Q: How common is BUB1B p.Lys94= (c.282G>A) in the general population?

BUB1B p.Lys94= (c.282G>A) is common (popmax 14.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.282G>A · rs1801389 · VCV257637

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 14.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

colorectal cancer

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 0.77	GERP -0.81, phastCons 1
Overall
CADD	7.858	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.5% European (non-Finnish) · 171,390/1,178,894 alleles

Filtering AF 14.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.5%

Overall 13.5% 217,698/1,612,750 alleles · common exomes 197,383/1,460,526 · genomes 20,315/152,224 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	20.8%	5
Ashkenazi Jewishnot grpmax-eligible	18.7%	5
Finnishnot grpmax-eligible	17.7%	6
European (non-Finnish)grpmax	14.5%	7
African / African-American	13.1%	8
Remaining individualsnot grpmax-eligible	13%	8
Middle Eastern	12.2%	8
Admixed American	8.16%	12
South Asian	6.06%	17
East Asian	0.422%	237

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys94=
Coding: c.282G>A
MANE Select: NM_001211
dbSNP: rs1801389
Type: single nucleotide variant
Location: chr15:40170579 (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 94: the bub1 n-terminal domain; an α-helix

Full BUB1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

colorectal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: premature chromatid separation trait mosaic variegated aneuploidy syndrome 1

Similar variants

BUB1B p.Lys94Arg 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-lys94 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown