Is BRPF1 p.Lys484Arg (c.1451A>G) pathogenic?

BRPF1 p.Lys484Arg (c.1451A>G) is classified Likely benign in BRPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.1205); Ultra-rare (popmax 0.0181%, amr); Associated with Inborn genetic diseases.

What condition is associated with BRPF1 p.Lys484Arg (c.1451A>G)?

BRPF1 p.Lys484Arg (c.1451A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BRPF1 p.Lys484Arg (c.1451A>G) in the general population?

BRPF1 p.Lys484Arg (c.1451A>G) is ultra-rare (popmax 0.0181%, amr) (gnomAD).

What do computational predictors say about BRPF1 p.Lys484Arg (c.1451A>G)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

BRPF1 p.Lys484Arg

c.1451A>G · rs139007155 · VCV2305410

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 205 bp · p 0.51 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% Admixed American · 10/55,140 alleles

Filtering AF 0.00984% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00745%

Overall 0.00515% 82/1,592,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0181%	5,514
European (non-Finnish)	0.00556%	17,989
African / African-American	0.00537%	18,632
East Asian	0.00228%	43,886
Remaining individualsnot grpmax-eligible	0.00162%	61,812
Finnishnot grpmax-eligible	0.00159%	62,874

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.Lys484Arg
Coding: c.1451A>G
MANE Select: NM_001003694
dbSNP: rs139007155
Type: single nucleotide variant
Location: chr3:9739850 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 484: the 'disordered' 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)

Full BRPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRPF1 p.Lys484Met Uncertain significance ★ ⚠ same residue
BRPF1 p.Arg182Trp Uncertain significance ★★ ⚠ same condition
BRPF1 p.Arg319His Uncertain significance ★★ ⚠ same condition
BRPF1 p.Asp445Asn Uncertain significance ★★ ⚠ same condition
BRPF1 p.Cys858Phe Uncertain significance ★★ ⚠ same condition
BRPF1 p.Glu1211Lys Uncertain significance ★★ ⚠ same condition
BRPF1 p.Leu777Val Uncertain significance ★★ ⚠ same condition
BRPF1 p.Lys585Asn Uncertain significance ★★ ⚠ same condition

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-lys484arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown