Is BUB1B p.Ile889= (c.2667T>C) pathogenic?

BUB1B p.Ile889= (c.2667T>C) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-15). Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ile889= (c.2667T>C)?

BUB1B p.Ile889= (c.2667T>C) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ile889= (c.2667T>C) in the general population?

BUB1B p.Ile889= (c.2667T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

BUB1B p.Ile889=

c.2667T>C · rs901161308 · VCV412523

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor gain, 11 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.44	GERP -0.24, phastCons 1
Overall
CADD	6.146	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,034 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00124% 20/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)grpmax	0.000254%	393,345

Ashkenazi Jewish 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.Ile889=
Coding: c.2667T>C
MANE Select: NM_001211
dbSNP: rs901161308
Type: single nucleotide variant
Location: chr15:40213463 (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 889: the protein kinase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mosaic variegated aneuploidy syndrome 1

Similar variants

BUB1B p.Ile889Met Uncertain significance ★ ⚠ same residue
BUB1B p.Ile889Phe 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

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-ile889 (accessed [today's date]).

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