Is BUB1B p.Arg244= (c.732T>A) pathogenic?

BUB1B p.Arg244= (c.732T>A) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-15). Very rare (popmax 0.005%, amr); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Arg244= (c.732T>A)?

BUB1B p.Arg244= (c.732T>A) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Arg244= (c.732T>A) in the general population?

BUB1B p.Arg244= (c.732T>A) is very rare (popmax 0.005%, amr) (gnomAD).

BUB1B p.Arg244=

c.732T>A · rs780852497 · VCV1130752

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -1.6, phastCons 0.001
Overall
CADD	9.558	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

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

Overall 0.00112% 18/1,613,948 alleles · very rare exomes 17/1,461,754 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
African / African-American	0.00133%	74,932
European (non-Finnish)	0.00119%	84,282

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.Arg244=
Coding: c.732T>A
MANE Select: NM_001211
dbSNP: rs780852497
Type: single nucleotide variant
Location: chr15:40183864 (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

Similar variants

BUB1B p.Arg244Cys Uncertain significance ★★ same residue
BUB1B p.Arg244His Uncertain significance ★★ same residue
BUB1B p.Arg244Leu Uncertain significance ★★ ⚠ same residue
BUB1B p.Arg244Pro Uncertain significance ★ ⚠ same residue
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

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-arg244 (accessed [today's date]).

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