Is BRD2 p.Glu500del (c.1497GGA[1]) pathogenic?

BRD2 p.Glu500del (c.1497GGA[1]) is classified Uncertain significance in BRD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2013-07-03). Low-frequency (popmax 4.82%, sas).

How common is BRD2 p.Glu500del (c.1497GGA[1]) in the general population?

BRD2 p.Glu500del (c.1497GGA[1]) is low-frequency (popmax 4.82%, sas) (gnomAD).

BRD2 p.Glu500del

c.1497GGA[1] · rs3918142 · VCV95243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.82%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -2.3
Overall
CADD	17.98	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.82% South Asian · 4,386/91,062 alleles

Filtering AF 4.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.65%

Overall 3.02% 48,728/1,612,630 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	15.6%	6
South Asiangrpmax	4.82%	21
Ashkenazi Jewishnot grpmax-eligible	4.32%	23
European (non-Finnish)	3.3%	30
Remaining individualsnot grpmax-eligible	2.97%	34
Middle Eastern	2.03%	49
Admixed American	1.15%	87
East Asian	0.827%	121
Finnishnot grpmax-eligible	0.776%	129
African / African-American	0.601%	167

Amish 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: BRD2
Protein: p.Glu500del
Coding: c.1497GGA[1]
MANE Select: NM_005104
dbSNP: rs3918142
Type: Microsatellite
Location: chr6:32977922 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 500: the 'disordered' region

Full BRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD2 p.Glu500Asp Uncertain significance ★ ⚠ same residue
BRD2 p.Glu497del Benign ★ 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/brd2-p-glu500del (accessed [today's date]).

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