Is BUB1B p.Arg349fs (c.1045del) pathogenic?

BUB1B p.Arg349fs (c.1045del) is classified Pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-02). Very rare (popmax 0.00446%, eas); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Arg349fs (c.1045del)?

BUB1B p.Arg349fs (c.1045del) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Arg349fs (c.1045del) in the general population?

BUB1B p.Arg349fs (c.1045del) is very rare (popmax 0.00446%, eas) (gnomAD).

BUB1B p.Arg349fs

c.1045del · rs770262148 · VCV1320272

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.01	GERP -1.5, phastCons 0.038

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,914 alleles · very rare exomes 2/1,461,578 · genomes 0/152,336 · joint denominator

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.Arg349fs
Coding: c.1045del
MANE Select: NM_001211
dbSNP: rs770262148
Type: Deletion
Location: chr15:40185629 (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 349: a UniProt-annotated variant site (in)

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.Arg349Gln Benign ★★ same residue
BUB1B p.Arg349= Benign ★ same residue
BUB1B p.Ala957fs Likely pathogenic ★★ same condition
BUB1B p.Arg80_Tyr81insTer Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.His856fs Pathogenic/Likely pathogenic ★★ same condition
BUB1B c.1628+24_1628+32del Likely benign ★★ same condition
BUB1B p.Ala332fs Likely pathogenic ★ same condition
BUB1B p.Arg104fs 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-arg349fs (accessed [today's date]).

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