Is BRPF1 p.Arg97His (c.290G>A) pathogenic?

BRPF1 p.Arg97His (c.290G>A) is classified Uncertain significance in BRPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-04). AlphaMissense: ambiguous (0.3888); Very rare (popmax 0.000169%, nfe).

How common is BRPF1 p.Arg97His (c.290G>A) in the general population?

BRPF1 p.Arg97His (c.290G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about BRPF1 p.Arg97His (c.290G>A)?

AlphaMissense predicts ambiguous (score 0.3888) — an in-silico prediction, not a clinical call.

BRPF1 p.Arg97His

c.290G>A · rs971945646 · VCV1310201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3888 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3888	ambiguous
REVEL	0.343	indeterminate
SaProt	LLR -11.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,121 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	28.3	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 0.000169% European (non-Finnish) · 2/1,180,034 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,886 alleles · very rare

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.Arg97His
Coding: c.290G>A
MANE Select: NM_001003694
dbSNP: rs971945646
Type: single nucleotide variant
Location: chr3:9734430 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 97: a UniProt-annotated variant site (in idddfp); the 'interaction with kat6a and kat6b' region

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

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-arg97his (accessed [today's date]).

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