Is BUB1B p.Ser738fs (c.2208_2211dup) pathogenic?

BUB1B p.Ser738fs (c.22082211dup) is classified Pathogenic in BUB1B (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-08). Very rare (popmax 0.00203%, nfe); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ser738fs (c.2208_2211dup)?

BUB1B p.Ser738fs (c.2208_2211dup) is associated with mosaic variegated aneuploidy syndrome 1, premature chromatid separation trait (ClinVar).

How common is BUB1B p.Ser738fs (c.2208_2211dup) in the general population?

BUB1B p.Ser738fs (c.2208_2211dup) is very rare (popmax 0.00203%, nfe) (gnomAD).

BUB1B p.Ser738fs

c.2208_2211dup · rs1392909108 · VCV6763

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,012 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00171% 25/1,461,854 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,167
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Ser738fs
Coding: c.2208_2211dup
MANE Select: NM_001211
dbSNP: rs1392909108
Type: Duplication
Location: chr15:40209697 (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: premature chromatid separation trait

Similar variants

BUB1B c.36-13dup Benign ★★ same condition
BUB1B p.Ala789fs Pathogenic ★ same condition
BUB1B p.Arg814fs Pathogenic ★ same condition
BUB1B p.Asn268fs Pathogenic ★ same condition
BUB1B p.Gly491fs Pathogenic ★ same condition
BUB1B p.His880fs Pathogenic ★ same condition
BUB1B p.Met300fs Pathogenic ★ same condition
BUB1B p.Ser191fs 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-ser738fs (accessed [today's date]).

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