Is BUB1B p.Ser191= (c.573C>A) pathogenic?

BUB1B p.Ser191= (c.573C>A) is classified Benign/Likely benign in BUB1B (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-13). Rare (popmax 0.247%, mid); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Ser191= (c.573C>A)?

BUB1B p.Ser191= (c.573C>A) is associated with Inborn genetic diseases, colorectal cancer, premature chromatid separation trait (ClinVar).

How common is BUB1B p.Ser191= (c.573C>A) in the general population?

BUB1B p.Ser191= (c.573C>A) is rare (popmax 0.247%, mid) (gnomAD).

BUB1B p.Ser191=

c.573C>A · rs138809057 · VCV465379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, mid)

Conditions

Inborn genetic diseases

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 -1.2	GERP -1
Overall
CADD	6.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% Middle Eastern · 15/6,082 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.0556% 897/1,613,758 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.564%	177
Middle Easterngrpmax	0.247%	405
Remaining individualsnot grpmax-eligible	0.0976%	1,024
Admixed American	0.0584%	1,714
European (non-Finnish)	0.0506%	1,976
African / African-American	0.028%	3,565
South Asian	0.0011%	91,052

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BUB1B
Protein: p.Ser191=
Coding: c.573C>A
MANE Select: NM_001211
dbSNP: rs138809057
Type: single nucleotide variant
Location: chr15:40176665 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.62 · 9 PDB
Residue 191: the bub1 n-terminal domain; an α-helix

Full BUB1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer premature chromatid separation trait mosaic variegated aneuploidy syndrome 1

Similar variants

BUB1B p.Ser191Phe Uncertain significance ★ ⚠ same residue
BUB1B p.Ser191Pro Uncertain significance ★ ⚠ same residue
BUB1B p.Ser191Tyr Uncertain significance ★ ⚠ same residue
BUB1B p.Ser191fs Pathogenic ★ same residue
BUB1B p.Arg114Ter Pathogenic ★★ same condition
BUB1B p.Arg120Ter Pathogenic ★★ same condition
BUB1B p.Arg194Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Arg199Ter Pathogenic/Likely pathogenic ★★ same condition

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/bub1b-p-ser191 (accessed [today's date]).

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