Is BUB3 p.Ala220= (c.660C>T) pathogenic?

BUB3 p.Ala220= (c.660C>T) is classified Likely benign in BUB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). Absent from gnomAD v4.1.

How common is BUB3 p.Ala220= (c.660C>T) in the general population?

BUB3 p.Ala220= (c.660C>T) is absent from gnomAD v4.1 (gnomAD).

BUB3 p.Ala220=

c.660C>T · rs2493765994 · VCV1754453

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.5	GERP 0.68, phastCons 1
Overall
CADD	15.14	PHRED · no single calibrated threshold — expert panels disagree

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: BUB3
Protein: p.Ala220=
Coding: c.660C>T
MANE Select: NM_004725
dbSNP: rs2493765994
Type: single nucleotide variant
Location: chr10:123162319 (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-ala220 (accessed [today's date]).

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