Is BUB1B p.Ser788fs (c.2363_2364del) pathogenic?

BUB1B p.Ser788fs (c.23632364del) is classified Pathogenic/Likely pathogenic in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-17). Very rare (popmax 0.00223%, eas); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ser788fs (c.2363_2364del)?

BUB1B p.Ser788fs (c.2363_2364del) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ser788fs (c.2363_2364del) in the general population?

BUB1B p.Ser788fs (c.2363_2364del) is very rare (popmax 0.00223%, eas) (gnomAD).

BUB1B p.Ser788fs

c.2363_2364del · rs756459860 · VCV986977

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, 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 18 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.8	GERP 2.2, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,810 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.00056% 9/1,608,336 alleles · very rare exomes 7/1,456,282 · genomes 2/152,054 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,784
East Asiangrpmax	0.00223%	44,810
African / African-American	0.00134%	74,718
European (non-Finnish)	0.000425%	235,027

Ashkenazi Jewish 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.Ser788fs
Coding: c.2363_2364del
MANE Select: NM_001211
dbSNP: rs756459860
Type: Microsatellite
Location: chr15:40210186 (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 788: the protein kinase domain

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.Ser788= Likely benign ★★ same residue
BUB1B p.Glu391del Uncertain significance ★★ same condition
BUB1B p.Lys438fs Pathogenic ★ same condition
BUB1B c.1568-15TC[2] Conflicting classifications of pathogenicity ★ same condition
BUB1B p.Glu215del Uncertain significance ★ same condition
BUB1B p.Lys540del Uncertain significance ★ same condition
BUB1B c.1058+8_1058+9del Likely benign ★ same condition
BUB1B c.1628+17_1628+24del Likely benign ★ 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-ser788fs (accessed [today's date]).

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