Is BRD1 p.Arg1014Trp (c.3040C>T) pathogenic?

BRD1 p.Arg1014Trp (c.3040C>T) is classified Uncertain significance in BRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: ambiguous (0.5554); Ultra-rare (popmax 0.0117%, amr).

How common is BRD1 p.Arg1014Trp (c.3040C>T) in the general population?

BRD1 p.Arg1014Trp (c.3040C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about BRD1 p.Arg1014Trp (c.3040C>T)?

AlphaMissense predicts ambiguous (score 0.5554) — an in-silico prediction, not a clinical call.

BRD1 p.Arg1014Trp

c.3040C>T · VCV3825495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5554 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
AlphaMissense	0.5554	ambiguous
REVEL	0.316	indeterminate
SaProt	LLR -10.06	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.47 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R883W vs ClinVar R1014W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,016 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00205% 33/1,613,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,574
African / African-American	0.00534%	18,740
East Asian	0.00446%	22,445
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
South Asian	0.0022%	45,547
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.00136%	73,751

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: BRD1
Protein: p.Arg1014Trp
Coding: c.3040C>T
MANE Select: NM_001304808
Type: single nucleotide variant
Location: chr22:49777115 (GRCh38)
Gene constraint: LOEUF 0.337 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.54 · 318 PDB
Residue 1014: an α-helix

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-arg1014trp (accessed [today's date]).

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