BRD4 p.Arg669His
c.2006G>A · rs35824241 · VCV2188855
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4277 | ambiguous |
|---|---|---|
| REVEL | 0.281 | benign-leaning |
| SaProt | LLR -11.83 | damaging |
| ⇒ SaProt calls this damaging; REVEL does not; AlphaMissense 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 | 28.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0266% | 3,766 |
| Admixed Americangrpmax | 0.00667% | 14,995 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 0.00254% | 39,332 |
| South Asian | 0.0011% | 91,082 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg669His
- Coding
- c.2006G>A
- MANE Select
- NM_001379291
- dbSNP
- rs35824241
- Type
- single nucleotide variant
- Location
- chr19:15255338 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 613 PDB
- Residue 669
- an α-helix; the net domain; a UniProt-annotated variant site (found in a patient with a neurodevelopmental syndrome; likely pathogenic); a UniProt-annotated variant site (in)
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-arg669his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown