Is BUB1B p.Ser191Tyr (c.572C>A) pathogenic?

BUB1B p.Ser191Tyr (c.572C>A) is classified Uncertain significance in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.1165); Very rare (popmax 0.00333%, amr); Associated with mosaic variegated aneuploidy syndrome 1.

What condition is associated with BUB1B p.Ser191Tyr (c.572C>A)?

BUB1B p.Ser191Tyr (c.572C>A) is associated with mosaic variegated aneuploidy syndrome 1 (ClinVar).

How common is BUB1B p.Ser191Tyr (c.572C>A) in the general population?

BUB1B p.Ser191Tyr (c.572C>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BUB1B p.Ser191Tyr (c.572C>A)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

BUB1B p.Ser191Tyr

c.572C>A · rs587778145 · VCV1018650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mosaic variegated aneuploidy syndrome 1

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -10.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 60 kb · p 0.0024 · regional, not allelic
Overall
CADD	23.4	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 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00041% 6/1,461,730 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,034
European (non-Finnish)	0.00017%	589,964

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.Ser191Tyr
Coding: c.572C>A
MANE Select: NM_001211
dbSNP: rs587778145
Type: single nucleotide variant
Location: chr15:40176664 (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

mosaic variegated aneuploidy syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BUB1B p.Ser191= Benign/Likely benign ★★ same residue
BUB1B p.Ser191Phe Uncertain significance ★ ⚠ same residue
BUB1B p.Ser191fs Pathogenic ★ same residue
BUB1B p.Ser191Pro Uncertain significance ★ ⚠ 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-ser191tyr (accessed [today's date]).

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