Is BRD4 p.Arg1282Cys (c.3844C>T) pathogenic?

BRD4 p.Arg1282Cys (c.3844C>T) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: ambiguous (0.5526); Ultra-rare (popmax 0.0169%, mid).

How common is BRD4 p.Arg1282Cys (c.3844C>T) in the general population?

BRD4 p.Arg1282Cys (c.3844C>T) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about BRD4 p.Arg1282Cys (c.3844C>T)?

AlphaMissense predicts ambiguous (score 0.5526) — an in-silico prediction, not a clinical call.

BRD4 p.Arg1282Cys

c.3844C>T · rs750347317 · VCV2868315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5526 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5526	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -12.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 321 bp · p 0.41 · regional, not allelic
Overall
CADD	28.8	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 0.0169% Middle Eastern · 1/5,918 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.00144% 23/1,596,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,918
African / African-American	0.0107%	9,317
Finnishnot grpmax-eligible	0.00341%	29,304
Remaining individualsnot grpmax-eligible	0.00162%	61,712
South Asian	0.00112%	89,222
European (non-Finnish)	0.000852%	117,346

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.Arg1282Cys
Coding: c.3844C>T
MANE Select: NM_001379291
dbSNP: rs750347317
Type: single nucleotide variant
Location: chr19:15238919 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 1282: the 'c-terminal (ctd) region' region; 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.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
BRD4 p.Glu1123Lys 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-arg1282cys (accessed [today's date]).

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