BRD4 p.Ser1074=
c.3222A>C · rs144097229 · VCV2157124
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0315%, 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 0.22 | GERP -0.7, phastCons 0.99 |
| Overall | ||
| CADD | 7.388 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0315%
European (non-Finnish) · 372/1,179,804 alleles
Filtering AF
0.0288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0278%
Overall
0.0244%
393/1,613,076 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0315% | 3,172 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,287 |
| Admixed American | 0.00167% | 59,938 |
| African / African-American | 0.00134% | 74,626 |
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.Ser1074=
- Coding
- c.3222A>C
- MANE Select
- NM_001379291
- dbSNP
- rs144097229
- Type
- single nucleotide variant
- Location
- chr19:15239970 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 613 PDB
- Residue 1074
- the 'disordered' region; the 'c-terminal (ctd) region' 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-ser1074 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown