Is BRD4 p.Pro974= (c.2922G>A) pathogenic?

BRD4 p.Pro974= (c.2922G>A) is classified Benign/Likely benign in BRD4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-01). Rare (popmax 0.204%, nfe).

How common is BRD4 p.Pro974= (c.2922G>A) in the general population?

BRD4 p.Pro974= (c.2922G>A) is rare (popmax 0.204%, nfe) (gnomAD).

BRD4 p.Pro974=

c.2922G>A · rs777234614 · VCV2073270

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.204%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	1.998	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.204% European (non-Finnish) · 682/334,158 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.146% 753/515,112 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.508%	197
European (non-Finnish)grpmax	0.204%	490
Remaining individualsnot grpmax-eligible	0.124%	807
Finnishnot grpmax-eligible	0.0701%	1,426
Admixed American	0.0413%	2,424
South Asian	0.0285%	3,504
African / African-American	0.0102%	9,765
East Asian	0.00618%	16,172

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro974=
Coding: c.2922G>A
MANE Select: NM_001379291
dbSNP: rs777234614
Type: single nucleotide variant
Location: chr19:15243147 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 974: 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.Pro974Leu Uncertain significance ★ ⚠ same residue
BRD4 p.Pro974Ser Uncertain significance ★ ⚠ same residue
BRD4 p.Pro974_Pro975insGlnGlnGln Uncertain significance ★ same residue
BRD4 p.Pro974_Pro975insLeuGlnGlnGlnPro 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

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-pro974 (accessed [today's date]).

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