Is BUB1B p.Ala332fs (c.995del) pathogenic?

BUB1B p.Ala332fs (c.995del) is classified Likely pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ala332fs (c.995del)?

BUB1B p.Ala332fs (c.995del) is associated with mosaic variegated aneuploidy syndrome 1, colorectal cancer, premature chromatid separation trait (ClinVar).

BUB1B p.Ala332fs

c.995del · VCV3577084

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.02	GERP -4.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BUB1B
Protein: p.Ala332fs
Coding: c.995del
MANE Select: NM_001211
Type: Deletion
Location: chr15:40185579 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.62 · 9 PDB

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

Disease context

mosaic variegated aneuploidy syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer premature chromatid separation trait

Similar variants

BUB1B p.Ala957fs Likely pathogenic ★★ same condition
BUB1B p.Arg80_Tyr81insTer Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.His856fs Pathogenic/Likely pathogenic ★★ same condition
BUB1B c.1628+24_1628+32del Likely benign ★★ same condition
BUB1B p.Arg104fs Pathogenic ★ same condition
BUB1B p.Arg349fs Pathogenic ★ same condition
BUB1B p.Arg381fs Pathogenic ★ same condition
BUB1B p.Glu63_Tyr64insTer 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-ala332fs (accessed [today's date]).

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