Is BRD4 p.Val193Leu (c.577G>C) pathogenic?

BRD4 p.Val193Leu (c.577G>C) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-20). AlphaMissense: likely benign (0.1183); Absent from gnomAD v4.1; Associated with BRD4-related disorder.

What condition is associated with BRD4 p.Val193Leu (c.577G>C)?

BRD4 p.Val193Leu (c.577G>C) is associated with BRD4-related disorder (ClinVar).

How common is BRD4 p.Val193Leu (c.577G>C) in the general population?

BRD4 p.Val193Leu (c.577G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD4 p.Val193Leu (c.577G>C)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

BRD4 p.Val193Leu

c.577G>C · rs202093296 · VCV2632926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BRD4-related disorder

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.18	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 0.4	GERP -0.94, phastCons 0.028
Regional constraint	o/e 1.06	unconstrained · MANE · 279 bp · p 0.47 · regional, not allelic
Overall
CADD	17.88	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

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.Val193Leu
Coding: c.577G>C
MANE Select: NM_001379291
dbSNP: rs202093296
Type: single nucleotide variant
Location: chr19:15265626 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 193: the 'disordered' region

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

Disease context

BRD4-related disorder

Similar variants

BRD4 p.Val193Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRD4 c.3282+2T>C Likely pathogenic ★ same condition
BRD4 p.Pro681Ser Uncertain significance ★ ⚠ same condition
BRD4 p.Thr210Ser Uncertain significance ★ ⚠ same condition
BRD4 p.Tyr390Cys Uncertain significance ★ ⚠ same condition
BRD4 p.Arg10Gly Uncertain significance ⚠ same condition
BRD4 p.Pro331Leu Uncertain significance ⚠ same condition
BRD4 p.Pro797Ser 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-val193leu (accessed [today's date]).

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