Is BUB1B p.Glu967= (c.2901A>G) pathogenic?

BUB1B p.Glu967= (c.2901A>G) is classified Likely benign in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-10). Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Glu967= (c.2901A>G)?

BUB1B p.Glu967= (c.2901A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Glu967= (c.2901A>G) in the general population?

BUB1B p.Glu967= (c.2901A>G) is very rare (popmax 0.005%, amr) (gnomAD).

BUB1B p.Glu967=

c.2901A>G · rs762290287 · VCV1797456

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

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 -0.31	GERP -2.6, phastCons 0.002
Overall
CADD	2.762	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,002 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,614,032 alleles · very rare exomes 2/1,461,792 · genomes 3/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,001
African / African-American	0.00267%	37,469

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.Glu967=
Coding: c.2901A>G
MANE Select: NM_001211
dbSNP: rs762290287
Type: single nucleotide variant
Location: chr15:40218506 (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 967: 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

Similar variants

BUB1B p.Glu967Asp 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-glu967 (accessed [today's date]).

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