BRD4 p.Lys543=
c.1629G>A · rs1246377221 · VCV3014911
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 0.18, phastCons 1 |
| Overall | ||
| CADD | 9.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,980 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000205%
3/1,460,718 alleles · very rare
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.Lys543=
- Coding
- c.1629G>A
- MANE Select
- NM_001379291
- dbSNP
- rs1246377221
- Type
- single nucleotide variant
- Location
- chr19:15256186 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 613 PDB
- Residue 543
- a UniProt-annotated variant site (found in a patient with a neurodevelopmental syndrome; likely pathogenic); the 'disordered' region; the 'bid region' region
Similar variants
- BRD4 p.Lys543Arg 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-lys543 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown