Is BUB1B p.Thr458fs (c.1372del) pathogenic?

BUB1B p.Thr458fs (c.1372del) is classified Likely pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-07). Absent from gnomAD; Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Thr458fs (c.1372del)?

BUB1B p.Thr458fs (c.1372del) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Thr458fs (c.1372del) in the general population?

BUB1B p.Thr458fs (c.1372del) is absent from gnomAD (gnomAD).

BUB1B p.Thr458fs

c.1372del · rs2542554942 · VCV2431740

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BUB1B
Protein: p.Thr458fs
Coding: c.1372del
MANE Select: NM_001211
dbSNP: rs2542554942
Type: Deletion
Location: chr15:40199696 (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 458: the 'disordered' region

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

Similar variants

BUB1B p.Thr458Ile Uncertain significance ★★ ⚠ same residue
BUB1B p.Thr458Ser Uncertain significance ★ ⚠ same residue
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.Ala332fs Likely pathogenic ★ same condition
BUB1B p.Arg104fs 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-thr458fs (accessed [today's date]).

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