Is BRD2 p.Ala474Val (c.1421C>T) pathogenic?

BRD2 p.Ala474Val (c.1421C>T) is classified Benign in BRD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-08). AlphaMissense: likely benign (0.0785); Low-frequency (popmax 4.44%, sas); Associated with BRD2-related disorder.

What condition is associated with BRD2 p.Ala474Val (c.1421C>T)?

BRD2 p.Ala474Val (c.1421C>T) is associated with BRD2-related disorder (ClinVar).

How common is BRD2 p.Ala474Val (c.1421C>T) in the general population?

BRD2 p.Ala474Val (c.1421C>T) is low-frequency (popmax 4.44%, sas) (gnomAD).

What do computational predictors say about BRD2 p.Ala474Val (c.1421C>T)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

BRD2 p.Ala474Val

c.1421C>T · rs3918143 · VCV3055955

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.44%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BRD2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.84	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 2.8	GERP -2.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 3,274 bp · p 0.26 · regional, not allelic
Overall
CADD	20.3	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 4.44% South Asian · 4,040/91,076 alleles

Filtering AF 4.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.28%

Overall 3.08% 49,606/1,613,002 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.44%	23
European (non-Finnish)	3.36%	30
Remaining individualsnot grpmax-eligible	2.83%	35
Admixed American	2.52%	40
East Asian	1.71%	58
Finnishnot grpmax-eligible	1.49%	67
Ashkenazi Jewishnot grpmax-eligible	1.29%	77
Amishnot grpmax-eligible	1.1%	91
Middle Eastern	1.04%	96
African / African-American	0.573%	174

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.Ala474Val
Coding: c.1421C>T
MANE Select: NM_005104
dbSNP: rs3918143
Type: single nucleotide variant
Location: chr6:32977848 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 169 PDB
Residue 474: a UniProt-annotated variant site (in); 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.Asp570= Benign same condition
BRD2 p.Lys31= Benign same condition
BRD2 p.Lys751= Likely benign same condition
BRD2 p.Ser603= 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-ala474val (accessed [today's date]).

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