Is BRD4 p.His1021Pro (c.3062A>C) pathogenic?

BRD4 p.His1021Pro (c.3062A>C) is classified Likely benign in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-01). AlphaMissense: likely benign (0.0644); Rare (popmax 0.954%, amr).

How common is BRD4 p.His1021Pro (c.3062A>C) in the general population?

BRD4 p.His1021Pro (c.3062A>C) is rare (popmax 0.954%, amr) (gnomAD).

What do computational predictors say about BRD4 p.His1021Pro (c.3062A>C)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

BRD4 p.His1021Pro

c.3062A>C · VCV3388299

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.954%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -0.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.2	GERP 0.86, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.05 · regional, not allelic
Overall
CADD	16.01	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 0.954% Admixed American · 64/6,706 alleles

Filtering AF 0.767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.699%

Overall 0.197% 444/225,862 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.954%	105
Ashkenazi Jewishnot grpmax-eligible	0.554%	181
African / African-American	0.532%	188
Finnishnot grpmax-eligible	0.319%	313
Middle Eastern	0.299%	335
East Asian	0.176%	567
South Asian	0.16%	626
European (non-Finnish)	0.144%	693
Remaining individualsnot grpmax-eligible	0.132%	759

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.His1021Pro
Coding: c.3062A>C
MANE Select: NM_001379291
Type: single nucleotide variant
Location: chr19:15243007 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 1021: 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.His1021Asn Benign ★★ ⚠ same residue
BRD4 p.His1021= Likely benign ★ same residue
BRD4 p.His1021_Pro1029del 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

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-his1021pro (accessed [today's date]).

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