Is BRD4 p.Gln517Pro (c.1550A>C) pathogenic?

BRD4 p.Gln517Pro (c.1550A>C) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-27). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BRD4 p.Gln517Pro (c.1550A>C)?

BRD4 p.Gln517Pro (c.1550A>C) is associated with Inborn genetic diseases (ClinVar).

How common is BRD4 p.Gln517Pro (c.1550A>C) in the general population?

BRD4 p.Gln517Pro (c.1550A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD4 p.Gln517Pro (c.1550A>C)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

BRD4 p.Gln517Pro

c.1550A>C · rs1555737887 · VCV520607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic · top 5% in BRD4
REVEL	0.555	indeterminate
SaProt	LLR -16.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 900 bp · p 0.74 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRD4
Protein: p.Gln517Pro
Coding: c.1550A>C
MANE Select: NM_001379291
dbSNP: rs1555737887
Type: single nucleotide variant
Location: chr19:15256965 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 517: 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-gln517pro (accessed [today's date]).

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