Is BUB1 p.Arg1070= (c.3210T>G) pathogenic?

BUB1 p.Arg1070= (c.3210T>G) is classified Likely benign in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-25). Very rare (popmax 0.00225%, eas).

How common is BUB1 p.Arg1070= (c.3210T>G) in the general population?

BUB1 p.Arg1070= (c.3210T>G) is very rare (popmax 0.00225%, eas) (gnomAD).

BUB1 p.Arg1070=

c.3210T>G · rs2467963171 · VCV1728939

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

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
Pangolin	Δ0.24	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.48
Overall
CADD	5.637	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% East Asian · 1/44,358 alleles

Overall 6.93e-05% 1/1,442,546 alleles · very rare

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: BUB1
Protein: p.Arg1070=
Coding: c.3210T>G
MANE Select: NM_004336
dbSNP: rs2467963171
Type: single nucleotide variant
Location: chr2:110638012 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 1070: the protein kinase domain; an α-helix

Full BUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB1 p.Arg1070Cys Uncertain significance ★★ ⚠ same residue
BUB1 p.Arg1070His Uncertain significance ★ ⚠ same residue
BUB1 p.Arg1070Leu Uncertain significance ★ ⚠ same residue
BUB1 p.Arg1070Pro Uncertain significance ★ ⚠ same residue
BUB1 c.1698+1G>T Uncertain significance ★★ same type
BUB1 p.Ala281Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala283Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala499Val 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/bub1-p-arg1070 (accessed [today's date]).

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