Is BRD2 p.Pro158Ala (c.472C>G) pathogenic?

BRD2 p.Pro158Ala (c.472C>G) is classified Uncertain significance in BRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely pathogenic (0.6358); Ultra-rare (popmax 0.0298%, afr).

How common is BRD2 p.Pro158Ala (c.472C>G) in the general population?

BRD2 p.Pro158Ala (c.472C>G) is ultra-rare (popmax 0.0298%, afr) (gnomAD).

What do computational predictors say about BRD2 p.Pro158Ala (c.472C>G)?

AlphaMissense predicts likely pathogenic (score 0.6358) — an in-silico prediction, not a clinical call.

BRD2 p.Pro158Ala

c.472C>G · rs777600975 · VCV2212554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6358 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0298%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6358	likely pathogenic
REVEL	0.769	pathogenic-leaning
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 3,664 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	24.9	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 0.0298% African / African-American · 22/73,940 alleles

Filtering AF 0.0201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.00175% 28/1,599,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0298%	3,361
Remaining individualsnot grpmax-eligible	0.00647%	15,466
Admixed American	0.00178%	56,256
European (non-Finnish)	8.51e-05%	1,175,527

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.Pro158Ala
Coding: c.472C>G
MANE Select: NM_005104
dbSNP: rs777600975
Type: single nucleotide variant
Location: chr6:32976031 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 158: the bromo 1 domain

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-pro158ala (accessed [today's date]).

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