Is BRPF1 p.Ile112Ser (c.335T>G) pathogenic?

BRPF1 p.Ile112Ser (c.335T>G) is classified Uncertain significance in BRPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-11). AlphaMissense: likely pathogenic (0.997); Absent from gnomAD v4.1.

How common is BRPF1 p.Ile112Ser (c.335T>G) in the general population?

BRPF1 p.Ile112Ser (c.335T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRPF1 p.Ile112Ser (c.335T>G)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

BRPF1 p.Ile112Ser

c.335T>G · VCV3572805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic
REVEL	0.775	moderately pathogenic-leaning
SaProt	LLR -11.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	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	25.4	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.

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.Ile112Ser
Coding: c.335T>G
MANE Select: NM_001003694
Type: single nucleotide variant
Location: chr3:9734475 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 112: 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.Ile112Val 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-ile112ser (accessed [today's date]).

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