Is BRD2 p.Lys751= (c.2253A>G) pathogenic?

BRD2 p.Lys751= (c.2253A>G) is classified Likely benign in BRD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-08). Very rare (popmax 0.00267%, afr); Associated with BRD2-related disorder.

What condition is associated with BRD2 p.Lys751= (c.2253A>G)?

BRD2 p.Lys751= (c.2253A>G) is associated with BRD2-related disorder (ClinVar).

How common is BRD2 p.Lys751= (c.2253A>G) in the general population?

BRD2 p.Lys751= (c.2253A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

BRD2 p.Lys751=

c.2253A>G · VCV3352605

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

BRD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -2.9, phastCons 1
Overall
CADD	7.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,930 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00205% 33/1,612,936 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,465
European (non-Finnish)	0.00254%	39,335
South Asian	0.0011%	91,088

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.Lys751=
Coding: c.2253A>G
MANE Select: NM_005104
Type: single nucleotide variant
Location: chr6:32980448 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 751: the 'disordered' region

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

Disease context

BRD2-related disorder

Similar variants

BRD2 c.334-10T>C Benign same condition
BRD2 c.472-5C>T Likely benign same condition
BRD2 p.Ala474Val Benign same condition
BRD2 p.Asp570= Benign same condition
BRD2 p.Lys31= Benign same condition
BRD2 p.Ser603= Benign same condition
BRD2 p.Tyr153= Likely benign same condition
BRD2 p.Pro12Leu Uncertain significance ★★ ⚠ 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-lys751 (accessed [today's date]).

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