Is BRD2 p.Tyr153= (c.459C>T) pathogenic?

BRD2 p.Tyr153= (c.459C>T) is classified Likely benign in BRD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-28). Rare (popmax 0.479%, mid); Associated with BRD2-related disorder.

What condition is associated with BRD2 p.Tyr153= (c.459C>T)?

BRD2 p.Tyr153= (c.459C>T) is associated with BRD2-related disorder (ClinVar).

How common is BRD2 p.Tyr153= (c.459C>T) in the general population?

BRD2 p.Tyr153= (c.459C>T) is rare (popmax 0.479%, mid) (gnomAD).

BRD2 p.Tyr153=

c.459C>T · rs571205164 · VCV3044768

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.479%, mid)

Conditions

BRD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.18	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.2	GERP -3.8
Overall
CADD	0.655	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.479% Middle Eastern · 29/6,054 alleles

Filtering AF 0.343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.297%

Overall 0.0104% 168/1,611,606 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.479%	209
South Asian	0.0828%	1,208
Remaining individualsnot grpmax-eligible	0.016%	6,246
European (non-Finnish)	0.00432%	23,129
Admixed American	0.00334%	29,937
East Asian	0.00223%	44,798

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.Tyr153=
Coding: c.459C>T
MANE Select: NM_005104
dbSNP: rs571205164
Type: single nucleotide variant
Location: chr6:32975509 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 153: the bromo 1 domain; an α-helix

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

Disease context

BRD2-related disorder

Similar variants

BRD2 p.Tyr153Cys Uncertain significance ★ ⚠ same residue
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.Lys751= Likely benign same condition
BRD2 p.Ser603= Benign 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/brd2-p-tyr153 (accessed [today's date]).

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