BRD4 p.Pro260=
c.780A>C · rs1449267256 · VCV2649487
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
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 -2.5 | GERP -4.9 |
| Overall | ||
| CADD | 1.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 8/42,770 alleles
Filtering AF
0.00921%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00678%
Overall
0.00216%
24/1,112,734 alleles · ultra-rare
exomes 3/1,041,664 · genomes 21/71,070 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,346 |
| Finnishnot grpmax-eligible | 0.0115% | 8,710 |
| East Asian | 0.00388% | 25,798 |
| Admixed American | 0.00238% | 42,024 |
| South Asian | 0.00137% | 72,898 |
| European (non-Finnish) | 0.00108% | 92,551 |
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.Pro260=
- Coding
- c.780A>C
- MANE Select
- NM_001379291
- dbSNP
- rs1449267256
- Type
- single nucleotide variant
- Location
- chr19:15265423 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 613 PDB
- Residue 260
- 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-pro260 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown