Is BUB1B p.Val920= (c.2760G>C) pathogenic?

BUB1B p.Val920= (c.2760G>C) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-07). Very rare (popmax 0.00267%, afr); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Val920= (c.2760G>C)?

BUB1B p.Val920= (c.2760G>C) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Val920= (c.2760G>C) in the general population?

BUB1B p.Val920= (c.2760G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

BUB1B p.Val920=

c.2760G>C · rs151035388 · VCV1079858

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -4.4
Overall
CADD	0.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,898 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,614,030 alleles · very rare exomes 22/1,461,874 · genomes 3/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,449
European (non-Finnish)	0.00186%	53,637
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Val920=
Coding: c.2760G>C
MANE Select: NM_001211
dbSNP: rs151035388
Type: single nucleotide variant
Location: chr15:40217577 (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 920: 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.Val920Gly Uncertain significance ★★ ⚠ same residue
BUB1B p.Val920Leu Uncertain significance ★ ⚠ same residue
BUB1B p.Val920Met Uncertain significance ★ ⚠ same residue
BUB1B p.Arg114Ter Pathogenic ★★ same condition
BUB1B p.Arg120Ter Pathogenic ★★ same condition
BUB1B p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg67Ter Pathogenic/Likely 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-val920 (accessed [today's date]).

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