Is BUB1B p.His193fs (c.578del) pathogenic?

BUB1B p.His193fs (c.578del) is classified Pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). Ultra-rare (popmax 0.0165%, mid); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.His193fs (c.578del)?

BUB1B p.His193fs (c.578del) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.His193fs (c.578del) in the general population?

BUB1B p.His193fs (c.578del) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

BUB1B p.His193fs

c.578del · rs1179465577 · VCV947291

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 5.8	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,613,948 alleles · ultra-rare exomes 1/1,461,642 · genomes 0/152,306 · 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.His193fs
Coding: c.578del
MANE Select: NM_001211
dbSNP: rs1179465577
Type: Deletion
Location: chr15:40176670 (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 193: 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.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
BUB1B p.Arg349fs Pathogenic ★ same condition
BUB1B p.Arg381fs 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-his193fs (accessed [today's date]).

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