Is BRD4 p.Glu408fs (c.1224delinsCA) pathogenic?

BRD4 p.Glu408fs (c.1224delinsCA) is classified Pathogenic in BRD4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-25). Absent from gnomAD; Associated with Cornelia de Lange syndrome 6.

What condition is associated with BRD4 p.Glu408fs (c.1224delinsCA)?

BRD4 p.Glu408fs (c.1224delinsCA) is associated with Cornelia de Lange syndrome 6 (ClinVar).

How common is BRD4 p.Glu408fs (c.1224delinsCA) in the general population?

BRD4 p.Glu408fs (c.1224delinsCA) is absent from gnomAD (gnomAD).

BRD4 p.Glu408fs

c.1224delinsCA · rs2512580369 · VCV2671881

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRD4
Protein: p.Glu408fs
Coding: c.1224delinsCA
MANE Select: NM_001379291
dbSNP: rs2512580369
Type: Indel
Location: chr19:15263537 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 408: an α-helix; the bromo 2 domain; 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.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
BRD4 c.285+1G>T Pathogenic ★ same condition
BRD4 p.Gln1105fs Likely pathogenic ★ same condition
BRD4 p.Gln910fs 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-glu408fs (accessed [today's date]).

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