Is BRD4 p.Pro786Ser (c.2356C>T) pathogenic?

BRD4 p.Pro786Ser (c.2356C>T) is classified Conflicting classifications of pathogenicity in BRD4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-10). AlphaMissense: likely benign (0.0932); Very rare (popmax 0.00246%, sas); Associated with Cornelia de Lange syndrome 6.

What condition is associated with BRD4 p.Pro786Ser (c.2356C>T)?

BRD4 p.Pro786Ser (c.2356C>T) is associated with Cornelia de Lange syndrome 6 (ClinVar).

How common is BRD4 p.Pro786Ser (c.2356C>T) in the general population?

BRD4 p.Pro786Ser (c.2356C>T) is very rare (popmax 0.00246%, sas) (gnomAD).

What do computational predictors say about BRD4 p.Pro786Ser (c.2356C>T)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

BRD4 p.Pro786Ser

c.2356C>T · rs763074040 · VCV1714034

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cornelia de Lange syndrome 6

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -0.087, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.05 · regional, not allelic
Overall
CADD	18.43	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% South Asian · 2/81,216 alleles

Filtering AF 0.000409% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000153%

Overall 0.000167% 2/1,201,062 alleles · very rare

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.Pro786Ser
Coding: c.2356C>T
MANE Select: NM_001379291
dbSNP: rs763074040
Type: single nucleotide variant
Location: chr19:15244456 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 786: 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.Pro786= Benign/Likely benign ★★ same residue
BRD4 p.Pro786Leu 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
BRD4 c.285+1G>T Pathogenic ★ same condition
BRD4 p.Lys678Ter 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-pro786ser (accessed [today's date]).

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