BRD4 p.Ala1245=
c.3735C>T · rs201209267 · VCV2068917
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 -14 | GERP -2.7 |
| Overall | ||
| CADD | 0.067 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,056 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00719%
Overall
0.0051%
82/1,608,212 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,019 |
| South Asian | 0.011% | 9,083 |
| Admixed American | 0.00667% | 14,983 |
| African / African-American | 0.00533% | 18,746 |
| European (non-Finnish) | 0.00483% | 20,692 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,801 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,544 |
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.Ala1245=
- Coding
- c.3735C>T
- MANE Select
- NM_001379291
- dbSNP
- rs201209267
- Type
- single nucleotide variant
- Location
- chr19:15239106 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 613 PDB
- Residue 1245
- the 'c-terminal (ctd) region' region; the 'disordered' region; a UniProt-annotated variant site (found in a patient with a neurodevelopmental syndrome; likely pathogenic)
Similar variants
- 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
- BRD4 p.Glu1123Lys 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-ala1245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown