Is BUB3 p.Arg158= (c.474A>G) pathogenic?

BUB3 p.Arg158= (c.474A>G) is classified Likely benign in BUB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-11). Ultra-rare (popmax 0.0174%, mid).

How common is BUB3 p.Arg158= (c.474A>G) in the general population?

BUB3 p.Arg158= (c.474A>G) is ultra-rare (popmax 0.0174%, mid) (gnomAD).

BUB3 p.Arg158=

c.474A>G · rs111376184 · VCV1742815

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, mid)

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 -2.1	GERP -5.2
Overall
CADD	2.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% Middle Eastern · 1/5,760 alleles

Overall 0.000205% 3/1,460,896 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0174%	5,760
African / African-American	0.00133%	74,956
European (non-Finnish)	8.48e-05%	1,179,856

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: BUB3
Protein: p.Arg158=
Coding: c.474A>G
MANE Select: NM_004725
dbSNP: rs111376184
Type: single nucleotide variant
Location: chr10:123160463 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.10

Full BUB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB3 p.Arg314= Likely benign ★★ same type
BUB3 p.Ser197= Likely benign ★★ same type
BUB3 p.Ser198= Likely benign ★★ same type
BUB3 p.Ala131Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala155Val Uncertain significance ★ ⚠ same type
BUB3 p.Ala187Gly Uncertain significance ★ ⚠ same type
BUB3 p.Ala239Gly Uncertain significance ★ ⚠ same type
BUB3 p.Ala292Val Uncertain significance ★ ⚠ same type

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/bub3-p-arg158 (accessed [today's date]).

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