Is BRPF1 p.Pro1106Ser (c.3316C>T) pathogenic?

BRPF1 p.Pro1106Ser (c.3316C>T) is classified Uncertain significance in BRPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is BRPF1 p.Pro1106Ser (c.3316C>T) in the general population?

BRPF1 p.Pro1106Ser (c.3316C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRPF1 p.Pro1106Ser (c.3316C>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

BRPF1 p.Pro1106Ser

c.3316C>T · rs2077118005 · VCV2574886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 7% in BRPF1
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -13.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 1,465 bp · p 2.7e-12 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 P1100S vs ClinVar P1106S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRPF1
Protein: p.Pro1106Ser
Coding: c.3316C>T
MANE Select: NM_001003694
dbSNP: rs2077118005
Type: single nucleotide variant
Location: chr3:9745922 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 1100 UniProt numbering: 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 UniProt-annotated variant site (in idddfp; no effect on histone h3-k23 acetylation; 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

Similar variants

BRPF1 p.Pro1106Ala Uncertain significance ⚠ same residue
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

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-pro1106ser (accessed [today's date]).

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