Is BRD4 p.Gln910fs (c.2728dup) pathogenic?

BRD4 p.Gln910fs (c.2728dup) is classified Likely pathogenic in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-08). Ultra-rare (popmax 0.0128%, eas); Associated with Cornelia de Lange syndrome 6.

What condition is associated with BRD4 p.Gln910fs (c.2728dup)?

BRD4 p.Gln910fs (c.2728dup) is associated with Cornelia de Lange syndrome 6 (ClinVar).

How common is BRD4 p.Gln910fs (c.2728dup) in the general population?

BRD4 p.Gln910fs (c.2728dup) is ultra-rare (popmax 0.0128%, eas) (gnomAD).

BRD4 p.Gln910fs

c.2728dup · rs868796773 · VCV2920709

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, eas)

Conditions

Cornelia de Lange syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP -0.11, phastCons 1
Overall
CADD	33.0	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 0.0128% East Asian · 1/7,824 alleles

Overall 0.000456% 4/877,984 alleles · ultra-rare exomes 3/858,200 · genomes 1/19,784 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0128%	7,824
Finnishnot grpmax-eligible	0.0051%	19,614
South Asian	0.00317%	31,506
European (non-Finnish)	0.000134%	747,094

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: BRD4
Protein: p.Gln910fs
Coding: c.2728dup
MANE Select: NM_001379291
dbSNP: rs868796773
Type: Duplication
Location: chr19:15243340 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 910: the 'disordered' region; a UniProt-annotated variant site (found in a patient with a neurodevelopmental syndrome; likely pathogenic)

Full BRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cornelia de Lange syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRD4 p.Gln256fs Pathogenic/Likely pathogenic ★★ same condition
BRD4 p.Pro568fs Likely pathogenic ★ same condition
BRD4 p.Val439fs Likely pathogenic ★ same condition
BRD4 p.Gln910= Likely benign ★ same residue
BRD4 p.Tyr430Cys Likely pathogenic ★★ same condition
BRD4 p.Thr295Pro Uncertain significance ★★ ⚠ same condition
BRD4 c.1552-1G>A Pathogenic ★ same condition
BRD4 c.2211+2T>C 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/brd4-p-gln910fs (accessed [today's date]).

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