Is BUB1B p.Ser928= (c.2784C>T) pathogenic?

BUB1B p.Ser928= (c.2784C>T) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-07). Rare (popmax 0.441%, eas); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser928= (c.2784C>T)?

BUB1B p.Ser928= (c.2784C>T) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ser928= (c.2784C>T) in the general population?

BUB1B p.Ser928= (c.2784C>T) is rare (popmax 0.441%, eas) (gnomAD).

BUB1B p.Ser928=

c.2784C>T · rs139066741 · VCV465376

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.441%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.6	GERP -4
Overall
CADD	5.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.441% East Asian · 198/44,886 alleles

Filtering AF 0.391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.371%

Overall 0.0134% 216/1,614,128 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.441%	227
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,934
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00167%	60,008
European (non-Finnish)	0.000678%	147,503

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.Ser928=
Coding: c.2784C>T
MANE Select: NM_001211
dbSNP: rs139066741
Type: single nucleotide variant
Location: chr15:40217601 (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 928: the protein kinase domain

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.Ser928Thr Uncertain significance ★★ ⚠ same residue
BUB1B p.Ser928Arg Uncertain significance ★ ⚠ same residue
BUB1B p.Ser928Gly 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
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-ser928 (accessed [today's date]).

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