Is BRPF1 p.Pro1088Ser (c.3262C>T) pathogenic?

BRPF1 p.Pro1088Ser (c.3262C>T) is classified Uncertain significance in BRPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-06). AlphaMissense: likely benign (0.0564); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BRPF1 p.Pro1088Ser (c.3262C>T)?

BRPF1 p.Pro1088Ser (c.3262C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BRPF1 p.Pro1088Ser (c.3262C>T) in the general population?

BRPF1 p.Pro1088Ser (c.3262C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRPF1 p.Pro1088Ser (c.3262C>T)?

AlphaMissense predicts likely benign (score 0.0564) — an in-silico prediction, not a clinical call.

BRPF1 p.Pro1088Ser

c.3262C>T · VCV3993200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0564 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,178)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0564	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.13	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 7.7	GERP 0.43, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 759 bp · p 0.35 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1082S vs ClinVar P1088S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,178). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRPF1
Protein: p.Pro1088Ser
Coding: c.3262C>T
MANE Select: NM_001003694
Type: single nucleotide variant
Location: chr3:9745868 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 1088: the pwwp domain; 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); a UniProt-annotated variant site (in idddfp; no effect on histone h3-k23 acetylation; increased aggregation in the cytoplasm; no effect on expression and assembly of the moz/morf complex); a β-strand

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.Pro1088Leu Likely benign ★ 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-pro1088ser (accessed [today's date]).

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