Is BRD2 p.Ala599Pro (c.1795G>C) pathogenic?

BRD2 p.Ala599Pro (c.1795G>C) is classified Benign in BRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0737); Low-frequency (popmax 1.45%, mid).

How common is BRD2 p.Ala599Pro (c.1795G>C) in the general population?

BRD2 p.Ala599Pro (c.1795G>C) is low-frequency (popmax 1.45%, mid) (gnomAD).

What do computational predictors say about BRD2 p.Ala599Pro (c.1795G>C)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

BRD2 p.Ala599Pro

c.1795G>C · rs55952113 · VCV720051

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.45%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.4, phastCons 0.78
Regional constraint	o/e 1.05	unconstrained · MANE · 3,274 bp · p 0.26 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.45% Middle Eastern · 88/6,054 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.313% 5,052/1,613,028 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.45%	69
South Asian	0.948%	106
Ashkenazi Jewishnot grpmax-eligible	0.79%	127
Remaining individualsnot grpmax-eligible	0.398%	251
Admixed American	0.382%	262
European (non-Finnish)	0.276%	363
African / African-American	0.139%	722
Finnishnot grpmax-eligible	0.035%	2,859
East Asian	0.0178%	5,610

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.Ala599Pro
Coding: c.1795G>C
MANE Select: NM_005104
dbSNP: rs55952113
Type: single nucleotide variant
Location: chr6:32978342 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 599: a UniProt-annotated variant site (in); the 'disordered' region

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

Similar variants

BRD2 p.Pro12Leu Uncertain significance ★★ ⚠ same type
BRD2 p.Ala766Thr Benign/Likely benign ★★ same type
BRD2 p.Gln533= Likely benign ★★ same type
BRD2 p.Leu383= Likely benign ★★ same type
BRD2 p.Ser397= Benign/Likely benign ★★ same type
BRD2 p.Val465= Likely benign ★★ same type
BRD2 p.Ala263Val Uncertain significance ★ ⚠ same type
BRD2 p.Ala295Pro 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-ala599pro (accessed [today's date]).

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