Is BUB1B p.Ser191fs (c.564_571dup) pathogenic?

BUB1B p.Ser191fs (c.564571dup) is classified Pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). Very rare (popmax 8.47e-05%, nfe); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ser191fs (c.564_571dup)?

BUB1B p.Ser191fs (c.564_571dup) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ser191fs (c.564_571dup) in the general population?

BUB1B p.Ser191fs (c.564_571dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

BUB1B p.Ser191fs

c.564_571dup · VCV3608325

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 5 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	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 8.47e-05% European (non-Finnish) · 1/1,179,986 alleles

Overall 0.000124% 2/1,614,106 alleles · very rare exomes 2/1,461,826 · genomes 0/152,280 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	8.47e-05%	1,179,986

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser191fs
Coding: c.564_571dup
MANE Select: NM_001211
Type: Duplication
Location: chr15:40176655 (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 191: the bub1 n-terminal domain; an α-helix

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.Ser191= Benign/Likely benign ★★ same residue
BUB1B p.Ser191Phe Uncertain significance ★ ⚠ same residue
BUB1B p.Ser191Tyr Uncertain significance ★ ⚠ same residue
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

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-ser191fs (accessed [today's date]).

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