Is BUB1B p.Gln195= (c.585A>G) pathogenic?

BUB1B p.Gln195= (c.585A>G) is classified Conflicting classifications of pathogenicity in BUB1B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-10). Very rare (popmax 0.00133%, afr); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Gln195= (c.585A>G)?

BUB1B p.Gln195= (c.585A>G) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Gln195= (c.585A>G) in the general population?

BUB1B p.Gln195= (c.585A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

BUB1B p.Gln195=

c.585A>G · rs1595518738 · VCV803065

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.50	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.31	GERP -3.7, phastCons 0.001
Overall
CADD	17.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,916 alleles

Overall 0.000186% 3/1,613,930 alleles · very rare exomes 2/1,461,756 · genomes 1/152,174 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
African / African-Americangrpmax	0.00133%	74,916

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.Gln195=
Coding: c.585A>G
MANE Select: NM_001211
dbSNP: rs1595518738
Type: single nucleotide variant
Location: chr15:40183717 (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 195: 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.Gln195Glu Uncertain significance ★★ ⚠ same residue
BUB1B p.Gln195His 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
BUB1B p.Gln267Ter 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-gln195 (accessed [today's date]).

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