Is BUB3 p.Ser197= (c.591C>T) pathogenic?

BUB3 p.Ser197= (c.591C>T) is classified Likely benign in BUB3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Rare (popmax 0.801%, amr).

How common is BUB3 p.Ser197= (c.591C>T) in the general population?

BUB3 p.Ser197= (c.591C>T) is rare (popmax 0.801%, amr) (gnomAD).

BUB3 p.Ser197=

c.591C>T · rs189428865 · VCV717245

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.801%, amr)

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 1.1	GERP -2.2, phastCons 1
Overall
CADD	7.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.801% Admixed American · 480/59,906 alleles

Filtering AF 0.742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.719%

Overall 0.0305% 493/1,613,760 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.801%	125
Remaining individualsnot grpmax-eligible	0.0176%	5,682
African / African-American	0.00133%	74,998
European (non-Finnish)	8.48e-05%	1,179,874

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: BUB3
Protein: p.Ser197=
Coding: c.591C>T
MANE Select: NM_004725
dbSNP: rs189428865
Type: single nucleotide variant
Location: chr10:123162250 (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.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
BUB3 p.Ala294Glu 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-ser197 (accessed [today's date]).

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