Is BRPF1 p.Ser394= (c.1182A>G) pathogenic?

BRPF1 p.Ser394= (c.1182A>G) is classified Likely benign in BRPF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). Very rare (popmax 0.0073%, nfe); Associated with BRPF1-related disorder.

What condition is associated with BRPF1 p.Ser394= (c.1182A>G)?

BRPF1 p.Ser394= (c.1182A>G) is associated with BRPF1-related disorder (ClinVar).

How common is BRPF1 p.Ser394= (c.1182A>G) in the general population?

BRPF1 p.Ser394= (c.1182A>G) is very rare (popmax 0.0073%, nfe) (gnomAD).

BRPF1 p.Ser394=

c.1182A>G · rs141374176 · VCV3057681

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0073%, 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 -0.41	GERP -3.7, phastCons 0.001
Overall
CADD	4.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0073% European (non-Finnish) · 86/1,178,706 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00558%

Overall 0.00564% 91/1,612,408 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0073%	13,706
Remaining individualsnot grpmax-eligible	0.00481%	20,806
African / African-American	0.00267%	37,458

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.Ser394=
Coding: c.1182A>G
MANE Select: NM_001003694
dbSNP: rs141374176
Type: single nucleotide variant
Location: chr3:9739581 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 394: a UniProt-annotated variant site (in idddfp); a β-strand

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

Disease context

BRPF1-related disorder

Similar variants

BRPF1 p.Ser394Leu Uncertain significance ★ ⚠ same residue
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

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-ser394 (accessed [today's date]).

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