Is BRD4 p.Asn582Ser (c.1745A>G) pathogenic?

BRD4 p.Asn582Ser (c.1745A>G) is classified Conflicting classifications of pathogenicity in BRD4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0516); Ultra-rare (popmax 0.0419%, sas); Associated with Inborn genetic diseases.

What condition is associated with BRD4 p.Asn582Ser (c.1745A>G)?

BRD4 p.Asn582Ser (c.1745A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BRD4 p.Asn582Ser (c.1745A>G) in the general population?

BRD4 p.Asn582Ser (c.1745A>G) is ultra-rare (popmax 0.0419%, sas) (gnomAD).

What do computational predictors say about BRD4 p.Asn582Ser (c.1745A>G)?

AlphaMissense predicts likely benign (score 0.0516) — an in-silico prediction, not a clinical call.

BRD4 p.Asn582Ser

c.1745A>G · rs201063437 · VCV1972903

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0419%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0516	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -4.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor loss · deltas
Constraint at this position
Conservation	phyloP -2.2	GERP -4.1
Regional constraint	o/e 1.09	unconstrained · MANE · 672 bp · p 0.42 · regional, not allelic
Overall
CADD	0.03	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 0.0419% South Asian · 38/90,800 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0276%

Overall 0.00323% 52/1,611,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0419%	2,389
Admixed American	0.00669%	14,945
East Asian	0.00446%	22,445
Remaining individualsnot grpmax-eligible	0.00161%	62,254
European (non-Finnish)	0.000593%	168,544

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.Asn582Ser
Coding: c.1745A>G
MANE Select: NM_001379291
dbSNP: rs201063437
Type: single nucleotide variant
Location: chr19:15256070 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 582: a UniProt-annotated variant site (found in a patient with a neurodevelopmental syndrome; likely pathogenic); the 'disordered' region

Full BRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same condition
BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same condition
BRD4 p.Gln32Arg Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu715Lys Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu718Gln Uncertain significance ★★ ⚠ same condition
BRD4 p.Gly6Ala Uncertain significance ★★ ⚠ same condition

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-asn582ser (accessed [today's date]).

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