Is BUB1B p.Gln34Ter (c.100C>T) pathogenic?

BUB1B p.Gln34Ter (c.100C>T) is classified Likely pathogenic in BUB1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-17). Very rare (popmax 0.000254%, nfe); Associated with BUB1B-related disorder.

What condition is associated with BUB1B p.Gln34Ter (c.100C>T)?

BUB1B p.Gln34Ter (c.100C>T) is associated with BUB1B-related disorder (ClinVar).

How common is BUB1B p.Gln34Ter (c.100C>T) in the general population?

BUB1B p.Gln34Ter (c.100C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

BUB1B p.Gln34Ter

c.100C>T · VCV4924213

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

BUB1B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 23
Splicing
SpliceAI	Δ0.95	donor gain · deltas
Pangolin	Δ0.80	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Overall
CADD	51.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,028 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,146 alleles · very rare exomes 3/1,461,878 · genomes 0/152,268 · joint denominator

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.Gln34Ter
Coding: c.100C>T
MANE Select: NM_001211
Type: single nucleotide variant
Location: chr15:40165117 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.62 · 9 PDB

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

Disease context

BUB1B-related disorder

Similar variants

BUB1B p.Gln34Arg Uncertain significance ★ ⚠ same residue
BUB1B p.Gln34Leu Uncertain significance ★ ⚠ same residue
BUB1B p.Gln34= Likely benign ★ same residue
BUB1B p.Arg67Ter Pathogenic/Likely pathogenic ★★ same condition
BUB1B c.2386-11A>G Conflicting classifications of pathogenicity ★ same condition
BUB1B p.Gly129Arg Uncertain significance ⚠ same condition
BUB1B c.1567+3G>A Likely benign same condition
BUB1B p.Gly929fs 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-gln34ter (accessed [today's date]).

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