Is BUB1B p.Tyr69= (c.207C>T) pathogenic?

BUB1B p.Tyr69= (c.207C>T) is classified Likely benign in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Tyr69= (c.207C>T)?

BUB1B p.Tyr69= (c.207C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BUB1B p.Tyr69= (c.207C>T) in the general population?

BUB1B p.Tyr69= (c.207C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

BUB1B p.Tyr69=

c.207C>T · VCV3262218

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.14	GERP -2.7
Overall
CADD	6.672	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00031% 5/1,613,914 alleles · very rare exomes 5/1,461,614 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
Admixed American	0.00333%	30,016

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.Tyr69=
Coding: c.207C>T
MANE Select: NM_001211
Type: single nucleotide variant
Location: chr15:40170089 (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 69: the bub1 n-terminal domain

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

Similar variants

BUB1B p.Tyr69Cys Uncertain significance ★★ ⚠ same residue
BUB1B c.35+4G>T Uncertain significance ★★ same condition
BUB1B p.Ala1017Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala1046Pro Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala108Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala171Pro Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala173Thr Uncertain significance ★★ ⚠ same condition
BUB1B p.Ala183Thr Uncertain significance ★★ ⚠ 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-tyr69 (accessed [today's date]).

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