BRD2 p.Leu396=
c.1188C>G · rs754277245 · VCV727914
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0969%, amr)
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 4.9 | GERP 0.88, phastCons 1 |
| Overall | ||
| CADD | 11.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0969%
Admixed American · 58/59,870 alleles
Filtering AF
0.0769%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0697%
Overall
0.00366%
59/1,610,152 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0969% | 1,032 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,378 |
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
- BRD2
- Protein
- p.Leu396=
- Coding
- c.1188C>G
- MANE Select
- NM_005104
- dbSNP
- rs754277245
- Type
- single nucleotide variant
- Location
- chr6:32976924 (GRCh38)
- Gene constraint
- LOEUF 0.28 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 65.70 · 169 PDB
- Residue 396
- the bromo 2 domain; an α-helix
Similar variants
- BRD2 p.Pro12Leu Uncertain significance ★★ ⚠ same type
- BRD2 p.Ala766Thr Benign/Likely benign ★★ same type
- BRD2 p.Gln533= Likely benign ★★ same type
- BRD2 p.Leu383= Likely benign ★★ same type
- BRD2 p.Ser397= Benign/Likely benign ★★ same type
- BRD2 p.Val465= Likely benign ★★ same type
- BRD2 p.Ala263Val Uncertain significance ★ ⚠ same type
- BRD2 p.Ala295Pro 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/brd2-p-leu396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown