Is BRD1 p.Pro1072Arg (c.3215C>G) pathogenic?

BRD1 p.Pro1072Arg (c.3215C>G) is classified Uncertain significance in BRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely pathogenic (0.9973); Absent from gnomAD v4.1.

How common is BRD1 p.Pro1072Arg (c.3215C>G) in the general population?

BRD1 p.Pro1072Arg (c.3215C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD1 p.Pro1072Arg (c.3215C>G)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

BRD1 p.Pro1072Arg

c.3215C>G · VCV3825500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic · top 6% in BRD1
REVEL	0.647	pathogenic-leaning
SaProt	LLR -13.05	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 1,892 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	31.0	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 P941R vs ClinVar P1072R) — 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: BRD1
Protein: p.Pro1072Arg
Coding: c.3215C>G
MANE Select: NM_001304808
Type: single nucleotide variant
Location: chr22:49776066 (GRCh38)
Gene constraint: LOEUF 0.337 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.54 · 318 PDB
Residue 941 UniProt numbering: the pwwp domain

Full BRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD1 c.1657-4C>T Likely benign ★★ same type
BRD1 p.Ala1053= Benign ★★ same type
BRD1 p.Ala730Thr Benign ★★ same type
BRD1 p.Arg1020= Benign ★★ same type
BRD1 p.Gly620= Likely benign ★★ same type
BRD1 p.Gly776Arg Benign ★★ same type
BRD1 p.Phe193= Benign ★★ same type
BRD1 p.Pro111= Benign ★★ 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/brd1-p-pro1072arg (accessed [today's date]).

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