Is BRD4 p.Ser619Ile (c.1856G>T) pathogenic?

BRD4 p.Ser619Ile (c.1856G>T) is classified Likely pathogenic in BRD4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2001-11-18). AlphaMissense: likely pathogenic (0.9983); Absent from gnomAD v4.1; Associated with Short stature.

What condition is associated with BRD4 p.Ser619Ile (c.1856G>T)?

BRD4 p.Ser619Ile (c.1856G>T) is associated with Short stature (ClinVar).

How common is BRD4 p.Ser619Ile (c.1856G>T) in the general population?

BRD4 p.Ser619Ile (c.1856G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD4 p.Ser619Ile (c.1856G>T)?

AlphaMissense predicts likely pathogenic (score 0.9983) — an in-silico prediction, not a clinical call.

BRD4 p.Ser619Ile

c.1856G>T · rs1568383758 · VCV599567

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Short stature

Computational evidence

Protein change
AlphaMissense	0.9983	likely pathogenic ✓ concordant with ClinVar · top 5% in BRD4
REVEL	0.629	indeterminate
SaProt	LLR -15.24	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 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 1,281 bp · p 8.7e-10 · regional, not allelic
Overall
CADD	27.5	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

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.Ser619Ile
Coding: c.1856G>T
MANE Select: NM_001379291
dbSNP: rs1568383758
Type: single nucleotide variant
Location: chr19:15255488 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 619: an α-helix; the net domain; 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

Short stature — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRD4 p.His77del Likely pathogenic ★ same condition
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-ser619ile (accessed [today's date]).

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