Is BRD4 p.Met132fs (c.394_395del) pathogenic?

BRD4 p.Met132fs (c.394395del) is classified Likely pathogenic in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). Associated with Cornelia de Lange syndrome 6.

What condition is associated with BRD4 p.Met132fs (c.394_395del)?

BRD4 p.Met132fs (c.394_395del) is associated with Cornelia de Lange syndrome 6 (ClinVar).

BRD4 p.Met132fs

c.394_395del · VCV3775476

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 3 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1

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

Variant & gene context

Gene: BRD4
Protein: p.Met132fs
Coding: c.394_395del
MANE Select: NM_001379291
Type: Deletion
Location: chr19:15268933 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 132: the bromo 1 domain; an α-helix

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.Gln1105fs Likely pathogenic ★ same condition
BRD4 p.Pro237fs Likely pathogenic ★ same condition
BRD4 p.His1021_Pro1029del Likely benign ★ same condition
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

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-met132fs (accessed [today's date]).

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