Is BUB1 p.Arg1020Ser (c.3060A>C) pathogenic?

BUB1 p.Arg1020Ser (c.3060A>C) is classified Uncertain significance in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely pathogenic (0.9062); Absent from gnomAD v4.1.

How common is BUB1 p.Arg1020Ser (c.3060A>C) in the general population?

BUB1 p.Arg1020Ser (c.3060A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BUB1 p.Arg1020Ser (c.3060A>C)?

AlphaMissense predicts likely pathogenic (score 0.9062) — an in-silico prediction, not a clinical call.

BUB1 p.Arg1020Ser

c.3060A>C · rs2467966967 · VCV1799367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9062 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9062	likely pathogenic · top 5% in BUB1
REVEL	0.187	benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.00043 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BUB1
Protein: p.Arg1020Ser
Coding: c.3060A>C
MANE Select: NM_004336
dbSNP: rs2467966967
Type: single nucleotide variant
Location: chr2:110639744 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 1020: the protein kinase domain

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

Similar variants

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
BUB1 p.Ala502Ser Uncertain significance ★★ ⚠ same type
BUB1 p.Ala630Gly Uncertain significance ★★ ⚠ same type
BUB1 p.Ala705Thr Uncertain significance ★★ ⚠ same type
BUB1 p.Ala797Gly 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-arg1020ser (accessed [today's date]).

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