Is BRD2 p.Ser603= (c.1809T>C) pathogenic?

BRD2 p.Ser603= (c.1809T>C) is classified Benign in BRD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 36.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with BRD2-related disorder.

What condition is associated with BRD2 p.Ser603= (c.1809T>C)?

BRD2 p.Ser603= (c.1809T>C) is associated with BRD2-related disorder (ClinVar).

BRD2 p.Ser603=

Q: How common is BRD2 p.Ser603= (c.1809T>C) in the general population?

BRD2 p.Ser603= (c.1809T>C) is common (popmax 36.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1809T>C · rs206781 · VCV3059565

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 36.4%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

BRD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.005	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.5, phastCons 0.001
Overall
CADD	4.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.4% European (non-Finnish) · 429,215/1,179,902 alleles

Filtering AF 36.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.2%

Overall 35% 564,179/1,612,632 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	51.4%	2
Amishnot grpmax-eligible	37.3%	3
European (non-Finnish)grpmax	36.4%	3
Middle Eastern	34.1%	3
Ashkenazi Jewishnot grpmax-eligible	33.8%	3
Remaining individualsnot grpmax-eligible	32.4%	3
South Asian	31.8%	3
Admixed American	28.1%	4
East Asian	21.1%	5
African / African-American	19.8%	5

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BRD2
Protein: p.Ser603=
Coding: c.1809T>C
MANE Select: NM_005104
dbSNP: rs206781
Type: single nucleotide variant
Location: chr6:32978356 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 603: the 'disordered' region

Full BRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BRD2-related disorder

Similar variants

BRD2 c.334-10T>C Benign same condition
BRD2 c.472-5C>T Likely benign same condition
BRD2 p.Ala474Val Benign same condition
BRD2 p.Asp570= Benign same condition
BRD2 p.Lys31= Benign same condition
BRD2 p.Lys751= Likely benign same condition
BRD2 p.Tyr153= Likely benign same condition
BRD2 p.Pro12Leu 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/brd2-p-ser603 (accessed [today's date]).

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