Is BUB1 p.Asn534Asp (c.1600A>G) pathogenic?

BUB1 p.Asn534Asp (c.1600A>G) is classified Likely benign in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). AlphaMissense: likely benign (0.1303); Rare (popmax 0.378%, eas).

How common is BUB1 p.Asn534Asp (c.1600A>G) in the general population?

BUB1 p.Asn534Asp (c.1600A>G) is rare (popmax 0.378%, eas) (gnomAD).

What do computational predictors say about BUB1 p.Asn534Asp (c.1600A>G)?

AlphaMissense predicts likely benign (score 0.1303) — an in-silico prediction, not a clinical call.

BUB1 p.Asn534Asp

c.1600A>G · rs36109304 · VCV2742681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1303 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.378%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1303	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -3.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 40 kb · p 0.00043 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.378% East Asian · 169/44,650 alleles

Filtering AF 0.332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.314%

Overall 0.0115% 185/1,604,932 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.378%	264
Remaining individualsnot grpmax-eligible	0.0177%	5,643
South Asian	0.00447%	22,383
European (non-Finnish)	8.5e-05%	1,175,948

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.Asn534Asp
Coding: c.1600A>G
MANE Select: NM_004336
dbSNP: rs36109304
Type: single nucleotide variant
Location: chr2:110657562 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 534: a UniProt-annotated variant site (in)

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

Similar variants

BUB1 p.Asn534= Likely benign ★ 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
BUB1 p.Ala502Ser Uncertain significance ★★ ⚠ same type
BUB1 p.Ala630Gly Uncertain significance ★★ ⚠ same type
BUB1 p.Ala705Thr 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-asn534asp (accessed [today's date]).

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