Is BUB1B p.Gly129= (c.387G>T) pathogenic?

BUB1B p.Gly129= (c.387G>T) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-07). Ultra-rare (popmax 0.0125%, nfe); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Gly129= (c.387G>T)?

BUB1B p.Gly129= (c.387G>T) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Gly129= (c.387G>T) in the general population?

BUB1B p.Gly129= (c.387G>T) is ultra-rare (popmax 0.0125%, nfe) (gnomAD).

BUB1B p.Gly129=

c.387G>T · rs149153123 · VCV1102948

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, nfe)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.8	GERP -4.2
Overall
CADD	3.831	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% European (non-Finnish) · 148/1,179,966 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.00942% 152/1,613,938 alleles · ultra-rare exomes 148/1,461,784 · genomes 4/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0125%	7,973
Remaining individualsnot grpmax-eligible	0.0032%	31,238
Admixed American	0.00167%	60,000
Finnishnot grpmax-eligible	0.00156%	64,030

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.Gly129=
Coding: c.387G>T
MANE Select: NM_001211
dbSNP: rs149153123
Type: single nucleotide variant
Location: chr15:40176479 (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 129: 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.Gly129Glu Uncertain significance ★ ⚠ same residue
BUB1B p.Gly129Val Uncertain significance ★ ⚠ same residue
BUB1B p.Gly129Arg 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-gly129 (accessed [today's date]).

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