Is BRD4 p.Pro311Leu (c.932C>T) pathogenic?

BRD4 p.Pro311Leu (c.932C>T) is classified Conflicting classifications of pathogenicity in BRD4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-10). AlphaMissense: likely benign (0.0832); Rare (popmax 0.144%, sas); Associated with Inborn genetic diseases.

What condition is associated with BRD4 p.Pro311Leu (c.932C>T)?

BRD4 p.Pro311Leu (c.932C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BRD4 p.Pro311Leu (c.932C>T) in the general population?

BRD4 p.Pro311Leu (c.932C>T) is rare (popmax 0.144%, sas) (gnomAD).

What do computational predictors say about BRD4 p.Pro311Leu (c.932C>T)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

BRD4 p.Pro311Leu

c.932C>T · rs45500091 · VCV2200887

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP -0.67, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 174 bp · p 0.5 · regional, not allelic
Overall
CADD	23.3	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 0.144% South Asian · 131/91,032 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0169% 273/1,613,494 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.144%	695
European (non-Finnish)	0.0113%	8,872
Remaining individualsnot grpmax-eligible	0.00961%	10,407
East Asian	0.00446%	22,437
Admixed American	0.00167%	60,024

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.Pro311Leu
Coding: c.932C>T
MANE Select: NM_001379291
dbSNP: rs45500091
Type: single nucleotide variant
Location: chr19:15264684 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 311: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRD4 p.Pro311Ala Uncertain significance ★ ⚠ same residue
BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same condition
BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same condition
BRD4 p.Gln32Arg Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu715Lys Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu718Gln Uncertain significance ★★ ⚠ 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-pro311leu (accessed [today's date]).

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