Is BUB1B p.Asp73= (c.219C>T) pathogenic?

BUB1B p.Asp73= (c.219C>T) is classified Likely benign in BUB1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-21). Ultra-rare (popmax 0.02%, afr); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Asp73= (c.219C>T)?

BUB1B p.Asp73= (c.219C>T) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Asp73= (c.219C>T) in the general population?

BUB1B p.Asp73= (c.219C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

BUB1B p.Asp73=

c.219C>T · rs548540749 · VCV705657

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, 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 0.37	GERP -2, phastCons 0.99
Overall
CADD	9.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/75,016 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.000929% 15/1,613,838 alleles · ultra-rare exomes 6/1,461,582 · genomes 9/152,256 · joint denominator

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.Asp73=
Coding: c.219C>T
MANE Select: NM_001211
dbSNP: rs548540749
Type: single nucleotide variant
Location: chr15:40170101 (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 73: the bub1 n-terminal 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.Asp73Gly Uncertain significance ★★ ⚠ same residue
BUB1B p.Asp73Asn 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-asp73 (accessed [today's date]).

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