Is BUB1B p.Glu391del (c.1168GAG[1]) pathogenic?

BUB1B p.Glu391del (c.1168GAG[1]) is classified Uncertain significance in BUB1B (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0749%, nfe); Associated with colorectal cancer.

What condition is associated with BUB1B p.Glu391del (c.1168GAG[1])?

BUB1B p.Glu391del (c.1168GAG[1]) is associated with colorectal cancer, premature chromatid separation trait, mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Glu391del (c.1168GAG[1]) in the general population?

BUB1B p.Glu391del (c.1168GAG[1]) is ultra-rare (popmax 0.0749%, nfe) (gnomAD).

BUB1B p.Glu391del

c.1168GAG[1] · rs778590557 · VCV403741

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0749%, nfe)

Conditions

colorectal cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.24	GERP -1.4, phastCons 0.99
Overall
CADD	14.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0749% European (non-Finnish) · 884/1,179,936 alleles

Filtering AF 0.0708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0691%

Overall 0.0594% 958/1,613,974 alleles · ultra-rare exomes 903/1,461,764 · genomes 55/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0749%	1,335
Admixed American	0.0633%	1,579
Remaining individualsnot grpmax-eligible	0.0464%	2,155
African / African-American	0.00933%	10,715

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.Glu391del
Coding: c.1168GAG[1]
MANE Select: NM_001211
dbSNP: rs778590557
Type: Microsatellite
Location: chr15:40196654 (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 391: the 'disordered' region

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.Ser788fs Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Lys438fs Pathogenic ★ same condition
BUB1B c.1568-15TC[2] Conflicting classifications of pathogenicity ★ same condition
BUB1B p.Glu215del Uncertain significance ★ same condition
BUB1B p.Glu391Gly Uncertain significance ★ ⚠ same residue
BUB1B p.Lys540del Uncertain significance ★ same condition
BUB1B c.1058+8_1058+9del Likely benign ★ same condition
BUB1B c.1628+17_1628+24del Likely benign ★ 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-glu391del (accessed [today's date]).

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