Is BUB1 p.Gln170fs (c.510_511del) pathogenic?

BUB1 p.Gln170fs (c.510511del) is classified Uncertain significance in BUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). Very rare (popmax 0.00366%, nfe).

How common is BUB1 p.Gln170fs (c.510_511del) in the general population?

BUB1 p.Gln170fs (c.510_511del) is very rare (popmax 0.00366%, nfe) (gnomAD).

BUB1 p.Gln170fs

c.510_511del · VCV3631058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00366%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	phastCons 0.35
Overall
CADD	24.7	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 0.00366% European (non-Finnish) · 43/1,176,292 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00292% 47/1,609,836 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00642%	15,586
European (non-Finnish)grpmax	0.00366%	27,356

Remaining individuals 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: BUB1
Protein: p.Gln170fs
Coding: c.510_511del
MANE Select: NM_004336
Type: Deletion
Location: chr2:110669509 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.91 · 11 PDB
Residue 170: the bub1 n-terminal domain

Full BUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BUB1 p.Gln170Glu Uncertain significance ★ ⚠ same residue
BUB1 p.Gln170His Uncertain significance ★ ⚠ same residue
BUB1 p.Gln503fs Uncertain significance ★ same type
BUB1 p.Lys1053fs Uncertain significance ★ same type
BUB1 c.1699-20del Likely benign ★ same type
BUB1 c.567+7del Likely benign ★ same type
BUB1 c.958-15del Likely benign ★ same type
BUB1 p.His1024fs Pathogenic same type

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/bub1-p-gln170fs (accessed [today's date]).

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