BRPF1 p.Phe681=
c.2043T>C · rs753904009 · VCV746141
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0646%, eas)
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 2.9 | GERP 0.82, phastCons 1 |
| Overall | ||
| CADD | 9.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0646%
East Asian · 29/44,902 alleles
Filtering AF
0.0461%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0399%
Overall
0.00198%
32/1,614,040 alleles · ultra-rare
exomes 30/1,461,882 · genomes 2/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0646% | 1,548 |
| Admixed American | 0.00167% | 60,000 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| South Asian | 0.0011% | 91,086 |
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
- BRPF1
- Protein
- p.Phe681=
- Coding
- c.2043T>C
- MANE Select
- NM_001003694
- dbSNP
- rs753904009
- Type
- single nucleotide variant
- Location
- chr3:9742985 (GRCh38)
- Gene constraint
- LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.74 · 66 PDB
- Residue 681
- the bromo domain; the 'interaction with meaf6 and ing5' region; the 'required for runx1 and runx2 transcriptional activation' region; a UniProt-annotated variant site (in idddfp); a UniProt-annotated variant site (in idddfp; decreased histone h3-k23 acetylation; increased localization to the nucleus; decreased expression and assembly of the moz/morf complex); an α-helix
Similar variants
- BRPF1 p.Arg1100Ter Pathogenic/Likely pathogenic ★★ same type
- BRPF1 p.Arg251Ter Pathogenic ★★ same type
- BRPF1 p.Arg455Ter Pathogenic ★★ same type
- BRPF1 p.Trp478Ter Pathogenic/Likely pathogenic ★★ same type
- BRPF1 p.Ala363Thr Uncertain significance ★★ ⚠ same type
- BRPF1 p.Ala601Thr Uncertain significance ★★ ⚠ same type
- BRPF1 p.Arg106Cys Uncertain significance ★★ ⚠ same type
- BRPF1 p.Arg157His 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/brpf1-p-phe681 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown