Is BUB1B p.Ala430= (c.1290C>T) pathogenic?

BUB1B p.Ala430= (c.1290C>T) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-05). Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ala430= (c.1290C>T)?

BUB1B p.Ala430= (c.1290C>T) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ala430= (c.1290C>T) in the general population?

BUB1B p.Ala430= (c.1290C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

BUB1B p.Ala430=

c.1290C>T · rs376379876 · VCV1131082

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.2	GERP -3.8
Overall
CADD	6.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,844 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00118% 19/1,612,830 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,948
African / African-American	0.00535%	18,705
Remaining individualsnot grpmax-eligible	0.0032%	31,222
Admixed American	0.00167%	59,984
European (non-Finnish)	0.000763%	131,020

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.Ala430=
Coding: c.1290C>T
MANE Select: NM_001211
dbSNP: rs376379876
Type: single nucleotide variant
Location: chr15:40199616 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.62 · 9 PDB

Full BUB1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mosaic variegated aneuploidy syndrome 1

Similar variants

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
BUB1B p.Leu737Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B c.2385+4G>C Uncertain significance ★★ 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-ala430 (accessed [today's date]).

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