Is BRPF1 p.Leu604= (c.1812C>T) pathogenic?

BRPF1 p.Leu604= (c.1812C>T) is classified Benign in BRPF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-24). Low-frequency (popmax 1.78%, nfe); Associated with BRPF1-related disorder.

What condition is associated with BRPF1 p.Leu604= (c.1812C>T)?

BRPF1 p.Leu604= (c.1812C>T) is associated with BRPF1-related disorder (ClinVar).

How common is BRPF1 p.Leu604= (c.1812C>T) in the general population?

BRPF1 p.Leu604= (c.1812C>T) is low-frequency (popmax 1.78%, nfe) (gnomAD).

BRPF1 p.Leu604=

c.1812C>T · rs73021442 · VCV3056900

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.78%, nfe)

Conditions

BRPF1-related disorder

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 2.8	GERP -3, phastCons 1
Overall
CADD	10.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.78% European (non-Finnish) · 20,969/1,175,234 alleles

Filtering AF 1.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.76%

Overall 1.48% 23,848/1,607,110 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.78%	56
Remaining individualsnot grpmax-eligible	1.3%	77
Finnishnot grpmax-eligible	1.08%	93
South Asian	0.87%	115
Admixed American	0.367%	272
Middle Eastern	0.314%	318
African / African-American	0.283%	353
East Asian	0.272%	368
Ashkenazi Jewishnot grpmax-eligible	0.0813%	1,230

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.Leu604=
Coding: c.1812C>T
MANE Select: NM_001003694
dbSNP: rs73021442
Type: single nucleotide variant
Location: chr3:9741397 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 604: 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)

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

Disease context

BRPF1-related disorder

Similar variants

BRPF1 p.Arg251Ter Pathogenic ★★ same condition
BRPF1 p.Arg455Ter Pathogenic ★★ same condition
BRPF1 p.Gln643His Uncertain significance ★★ ⚠ same condition
BRPF1 p.Tyr1149Cys Uncertain significance ★★ ⚠ same condition
BRPF1 c.2921-1G>C Likely pathogenic ★ same condition
BRPF1 p.Pro1130Leu Likely pathogenic ★ same condition
BRPF1 p.Tyr1105Ter Likely pathogenic ★ same condition
BRPF1 p.Arg520Gly 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-leu604 (accessed [today's date]).

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