Is BUB1B p.Arg550Gln (c.1649G>A) pathogenic?

BUB1B p.Arg550Gln (c.1649G>A) is classified Benign/Likely benign in BUB1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0657); Low-frequency (popmax 1.26%, eas); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Arg550Gln (c.1649G>A)?

BUB1B p.Arg550Gln (c.1649G>A) is associated with mosaic variegated aneuploidy syndrome 1, premature chromatid separation trait (ClinVar).

How common is BUB1B p.Arg550Gln (c.1649G>A) in the general population?

BUB1B p.Arg550Gln (c.1649G>A) is low-frequency (popmax 1.26%, eas) (gnomAD).

What do computational predictors say about BUB1B p.Arg550Gln (c.1649G>A)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

BUB1B p.Arg550Gln

c.1649G>A · rs28989187 · VCV6766

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.26%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.8	GERP -4.2
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	0.009	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 1.26% East Asian · 564/44,864 alleles

Filtering AF 1.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.14%

Overall 0.0383% 618/1,613,904 alleles · low-frequency exomes 508/1,461,820 · genomes 110/152,084 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.26%	80
Remaining individualsnot grpmax-eligible	0.064%	1,562
Admixed American	0.00667%	14,994
South Asian	0.00329%	30,361
African / African-American	0.00267%	37,482
European (non-Finnish)	0.000424%	235,993

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.Arg550Gln
Coding: c.1649G>A
MANE Select: NM_001211
dbSNP: rs28989187
Type: single nucleotide variant
Location: chr15:40202609 (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 550: a UniProt-annotated variant site (in mva1; heterozygous compound with nonsense mutation)

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: premature chromatid separation trait

Similar variants

BUB1B p.Arg550Ter Pathogenic ★ same residue
BUB1B p.Arg550Gly Uncertain significance ★ ⚠ same residue
BUB1B p.Arg550= Likely benign ★ 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
BUB1B p.Arg67Ter 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-arg550gln (accessed [today's date]).

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