Is BRD4 p.Ala262Thr (c.784G>A) pathogenic?

BRD4 p.Ala262Thr (c.784G>A) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.069); Very rare (popmax 0.00728%, sas); Associated with Inborn genetic diseases.

What condition is associated with BRD4 p.Ala262Thr (c.784G>A)?

BRD4 p.Ala262Thr (c.784G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BRD4 p.Ala262Thr (c.784G>A) in the general population?

BRD4 p.Ala262Thr (c.784G>A) is very rare (popmax 0.00728%, sas) (gnomAD).

What do computational predictors say about BRD4 p.Ala262Thr (c.784G>A)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

BRD4 p.Ala262Thr

c.784G>A · rs1483781735 · VCV2260284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00728%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -4.9
Regional constraint	o/e 1.06	unconstrained · MANE · 279 bp · p 0.47 · regional, not allelic
Overall
CADD	7.218	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00728% South Asian · 5/68,656 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.00228% 21/920,924 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00728%	13,731
Remaining individualsnot grpmax-eligible	0.00606%	16,510
Admixed American	0.00484%	20,678
Finnishnot grpmax-eligible	0.00288%	34,720
African / African-American	0.00219%	45,754
European (non-Finnish)	0.00152%	65,770

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.Ala262Thr
Coding: c.784G>A
MANE Select: NM_001379291
dbSNP: rs1483781735
Type: single nucleotide variant
Location: chr19:15265419 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 262: 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

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-ala262thr (accessed [today's date]).

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