Is BRD4 p.Ala792Glu (c.2375C>A) pathogenic?

BRD4 p.Ala792Glu (c.2375C>A) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.2402); Absent from gnomAD v4.1.

How common is BRD4 p.Ala792Glu (c.2375C>A) in the general population?

BRD4 p.Ala792Glu (c.2375C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD4 p.Ala792Glu (c.2375C>A)?

AlphaMissense predicts likely benign (score 0.2402) — an in-silico prediction, not a clinical call.

BRD4 p.Ala792Glu

c.2375C>A · rs967021402 · VCV2127813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2402 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,570,462)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2402	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP -0.042, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.05 · regional, not allelic
Overall
CADD	16.73	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

No allele count reported in gnomAD v4.1 (AN 1,570,462). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRD4
Protein: p.Ala792Glu
Coding: c.2375C>A
MANE Select: NM_001379291
dbSNP: rs967021402
Type: single nucleotide variant
Location: chr19:15244437 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 792: 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.Ala792Val Uncertain significance ★ ⚠ 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
BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same type
BRD4 p.Gln32Arg 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-ala792glu (accessed [today's date]).

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