Is BUB1B p.Tyr116= (c.348T>C) pathogenic?

BUB1B p.Tyr116= (c.348T>C) is classified Benign/Likely benign in BUB1B (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.45%, mid); Associated with Inborn genetic diseases.

What condition is associated with BUB1B p.Tyr116= (c.348T>C)?

BUB1B p.Tyr116= (c.348T>C) is associated with Inborn genetic diseases, colorectal cancer, premature chromatid separation trait (ClinVar).

How common is BUB1B p.Tyr116= (c.348T>C) in the general population?

BUB1B p.Tyr116= (c.348T>C) is low-frequency (popmax 1.45%, mid) (gnomAD).

BUB1B p.Tyr116=

c.348T>C · rs28989189 · VCV238666

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.45%, 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 -0.52	GERP -2.3
Overall
CADD	5.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.45% Middle Eastern · 88/6,056 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.932% 15,045/1,613,708 alleles · low-frequency exomes 14,127/1,461,382 · genomes 918/152,326 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.45%	69
Ashkenazi Jewishnot grpmax-eligible	1.38%	73
European (non-Finnish)	1.08%	93
Remaining individualsnot grpmax-eligible	0.903%	111
South Asian	0.797%	125
Amishnot grpmax-eligible	0.439%	228
Finnishnot grpmax-eligible	0.35%	286
Admixed American	0.338%	296
African / African-American	0.173%	577
East Asian	0.00446%	22,406

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.Tyr116=
Coding: c.348T>C
MANE Select: NM_001211
dbSNP: rs28989189
Type: single nucleotide variant
Location: chr15:40170645 (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 116: 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

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

Similar variants

BUB1B p.Tyr116Cys 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
BUB1B p.Arg67Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B p.Gln267Ter Pathogenic ★★ same condition
BUB1B p.Leu737Ter 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-tyr116 (accessed [today's date]).

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