Is BUB1B c.239+2T>C pathogenic?

BUB1B c.239+2T>C is classified Likely pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). Very rare (popmax 8.49e-05%, nfe); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B c.239+2T>C?

BUB1B c.239+2T>C is associated with mosaic variegated aneuploidy syndrome 1, colorectal cancer, premature chromatid separation trait (ClinVar).

How common is BUB1B c.239+2T>C in the general population?

BUB1B c.239+2T>C is very rare (popmax 8.49e-05%, nfe) (gnomAD).

BUB1B c.239+2T>C

VCV3577080

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
REVEL	0.147	moderately benign-leaning
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.97	donor loss · deltas
Pangolin	Δ0.88	loss · gain 0.26 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.1	GERP 2.1, phastCons 1
Non-coding constraint	Z 0.98	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,874 alleles

Overall 6.85e-05% 1/1,459,526 alleles · very rare

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
Coding: c.239+2T>C
MANE Select: NM_001211
Type: single nucleotide variant
Location: chr15:40170123 (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.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
BUB1B p.Leu737Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B c.2385+4G>C 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-c-239-plus-2t-c (accessed [today's date]).

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