Is BUB3 p.Ser146= (c.438T>C) pathogenic?

BUB3 p.Ser146= (c.438T>C) is classified Likely benign in BUB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-21). Absent from gnomAD v4.1.

How common is BUB3 p.Ser146= (c.438T>C) in the general population?

BUB3 p.Ser146= (c.438T>C) is absent from gnomAD v4.1 (gnomAD).

BUB3 p.Ser146=

c.438T>C · rs2493763122 · VCV1740222

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	<0.2	all four deltas below 0.2 · T>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.2	GERP -5.2
Overall
CADD	5.037	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.Ser146=
Coding: c.438T>C
MANE Select: NM_004725
dbSNP: rs2493763122
Type: single nucleotide variant
Location: chr10:123160427 (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.Ser146Pro Uncertain significance ★ ⚠ same residue
BUB3 p.Ser146Thr Uncertain significance ★ ⚠ same residue
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

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-ser146 (accessed [today's date]).

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