Is BRD4 p.Pro252Arg (c.755C>G) pathogenic?

BRD4 p.Pro252Arg (c.755C>G) is classified Benign/Likely benign in BRD4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.168); Rare (popmax 0.132%, nfe).

How common is BRD4 p.Pro252Arg (c.755C>G) in the general population?

BRD4 p.Pro252Arg (c.755C>G) is rare (popmax 0.132%, nfe) (gnomAD).

What do computational predictors say about BRD4 p.Pro252Arg (c.755C>G)?

AlphaMissense predicts likely benign (score 0.168) — an in-silico prediction, not a clinical call.

BRD4 p.Pro252Arg

c.755C>G · rs200633797 · VCV1568249

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.168 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.168	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -11.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 279 bp · p 0.47 · regional, not allelic
Overall
CADD	20.3	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 0.132% European (non-Finnish) · 1,529/1,155,888 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.11% 1,719/1,569,346 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.132%	756
South Asian	0.12%	832
Remaining individualsnot grpmax-eligible	0.0909%	1,101
Middle Eastern	0.0803%	1,246
African / African-American	0.0296%	3,384
Admixed American	0.00703%	14,228
Finnishnot grpmax-eligible	0.00493%	20,288
Ashkenazi Jewishnot grpmax-eligible	0.0038%	26,346

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.Pro252Arg
Coding: c.755C>G
MANE Select: NM_001379291
dbSNP: rs200633797
Type: single nucleotide variant
Location: chr19:15265448 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 252: 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.Pro252Ser Uncertain significance ★ ⚠ same residue
BRD4 p.Pro252= 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

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-pro252arg (accessed [today's date]).

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