Is BRD1 p.Arg980Cys (c.2938C>T) pathogenic?

BRD1 p.Arg980Cys (c.2938C>T) is classified Uncertain significance in BRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: ambiguous (0.3966); Very rare (popmax 0.00534%, afr).

How common is BRD1 p.Arg980Cys (c.2938C>T) in the general population?

BRD1 p.Arg980Cys (c.2938C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about BRD1 p.Arg980Cys (c.2938C>T)?

AlphaMissense predicts ambiguous (score 0.3966) — an in-silico prediction, not a clinical call.

BRD1 p.Arg980Cys

c.2938C>T · VCV3825497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3966	ambiguous
REVEL	0.178	moderately benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.47 · regional, not allelic
Overall
CADD	32.0	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 R849C vs ClinVar R980C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,854 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00137% 22/1,607,136 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,713
Remaining individualsnot grpmax-eligible	0.00482%	20,749
Admixed American	0.00168%	59,522
European (non-Finnish)	0.00119%	84,149

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.Arg980Cys
Coding: c.2938C>T
MANE Select: NM_001304808
Type: single nucleotide variant
Location: chr22:49777733 (GRCh38)
Gene constraint: LOEUF 0.337 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.54 · 318 PDB
Residue 980: 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-arg980cys (accessed [today's date]).

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