BRPF1 p.Pro518fs
c.1547dup · VCV4056932
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 14 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- BRPF1
- Protein
- p.Pro518fs
- Coding
- c.1547dup
- MANE Select
- NM_001003694
- Type
- Duplication
- Location
- chr3:9739945 (GRCh38)
- Gene constraint
- LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.74 · 66 PDB
- Residue 518
- the 'interaction with meaf6 and ing5' 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)
Similar variants
- BRPF1 p.Pro518Leu Uncertain significance ★ same residue
- BRPF1 p.Tyr406Ter Pathogenic/Likely pathogenic ★★ same type
- BRPF1 p.Ala856delinsGlyTer Pathogenic ★ same type
- BRPF1 p.Arg593fs Pathogenic ★ same type
- BRPF1 p.Cys515fs Pathogenic ★ same type
- BRPF1 p.Glu1008Ter Pathogenic ★ same type
- BRPF1 p.Glu689fs Likely pathogenic ★ same type
- BRPF1 p.His164fs Pathogenic ★ 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-pro518fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown