Is BUB1B p.Arg244Cys (c.730C>T) pathogenic?

BUB1B p.Arg244Cys (c.730C>T) is classified Uncertain significance in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-13). AlphaMissense: ambiguous (0.519); Very rare (popmax 0.00667%, afr); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Arg244Cys (c.730C>T)?

BUB1B p.Arg244Cys (c.730C>T) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Arg244Cys (c.730C>T) in the general population?

BUB1B p.Arg244Cys (c.730C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about BUB1B p.Arg244Cys (c.730C>T)?

AlphaMissense predicts ambiguous (score 0.519) — an in-silico prediction, not a clinical call.

BUB1B p.Arg244Cys

c.730C>T · rs867444045 · VCV1389806

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.519	ambiguous
REVEL	0.393	indeterminate
SaProt	LLR -8.94	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,916 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000744% 12/1,613,928 alleles · very rare exomes 9/1,461,740 · genomes 3/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,983
Admixed American	0.00167%	60,002
European (non-Finnish)	0.000509%	196,656

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.Arg244Cys
Coding: c.730C>T
MANE Select: NM_001211
dbSNP: rs867444045
Type: single nucleotide variant
Location: chr15:40183862 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mosaic variegated aneuploidy syndrome 1

Similar variants

BUB1B p.Arg244His Uncertain significance ★★ same residue
BUB1B p.Arg244Leu Uncertain significance ★★ ⚠ same residue
BUB1B p.Arg244= Likely benign ★★ 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-arg244cys (accessed [today's date]).

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