Is BRD4 p.Pro731Leu (c.2192C>T) pathogenic?

BRD4 p.Pro731Leu (c.2192C>T) is classified Benign in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0791); Rare (popmax 0.403%, afr).

How common is BRD4 p.Pro731Leu (c.2192C>T) in the general population?

BRD4 p.Pro731Leu (c.2192C>T) is rare (popmax 0.403%, afr) (gnomAD).

What do computational predictors say about BRD4 p.Pro731Leu (c.2192C>T)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

BRD4 p.Pro731Leu

c.2192C>T · rs149185763 · VCV2066993

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.403%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.13	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 12	GERP -0.072, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.05 · regional, not allelic
Overall
CADD	23.7	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 0.403% African / African-American · 302/75,022 alleles

Filtering AF 0.365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.351%

Overall 0.0236% 381/1,614,130 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.403%	248
Admixed American	0.065%	1,539
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.032%	3,125
European (non-Finnish)	0.00144%	69,414
South Asian	0.0011%	91,086

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.Pro731Leu
Coding: c.2192C>T
MANE Select: NM_001379291
dbSNP: rs149185763
Type: single nucleotide variant
Location: chr19:15244729 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 731: 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

Similar variants

BRD4 p.Pro731= Likely benign ★ same residue
BRD4 p.Tyr430Cys Likely pathogenic ★★ same type
BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same type
BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same type
BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same type
BRD4 p.Asp337Asn Uncertain significance ★★ ⚠ same type
BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same type
BRD4 p.Gln32Arg Uncertain significance ★★ ⚠ same type

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-pro731leu (accessed [today's date]).

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