Is BUB1B p.Gln181= (c.543G>A) pathogenic?

BUB1B p.Gln181= (c.543G>A) is classified Likely benign in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-02). Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Gln181= (c.543G>A)?

BUB1B p.Gln181= (c.543G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Gln181= (c.543G>A) in the general population?

BUB1B p.Gln181= (c.543G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

BUB1B p.Gln181=

c.543G>A · rs2542524296 · VCV1747547

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

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 0.3	GERP -2.2, phastCons 0.94
Overall
CADD	4.419	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 0.000137% 2/1,461,842 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,180,012

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.Gln181=
Coding: c.543G>A
MANE Select: NM_001211
dbSNP: rs2542524296
Type: single nucleotide variant
Location: chr15:40176635 (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 181: the bub1 n-terminal domain; the 'necessary for interaction with knl1' region

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

Similar variants

BUB1B p.Gln181Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BUB1B p.Gln181Lys Uncertain significance ★ ⚠ same residue
BUB1B p.Gln181Pro Uncertain significance ★ ⚠ same residue
BUB1B c.35+4G>T Uncertain significance ★★ same condition
BUB1B p.Ala1017Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala1046Pro Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala108Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala171Pro 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-gln181 (accessed [today's date]).

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