Is BRD4 p.Ile820Val (c.2458A>G) pathogenic?

BRD4 p.Ile820Val (c.2458A>G) is classified Conflicting classifications of pathogenicity in BRD4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-01). AlphaMissense: likely benign (0.0737); Ultra-rare (popmax 0.0327%, nfe).

How common is BRD4 p.Ile820Val (c.2458A>G) in the general population?

BRD4 p.Ile820Val (c.2458A>G) is ultra-rare (popmax 0.0327%, nfe) (gnomAD).

What do computational predictors say about BRD4 p.Ile820Val (c.2458A>G)?

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

BRD4 p.Ile820Val

c.2458A>G · rs202038315 · VCV2912502

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0327%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.49	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 4.8	GERP -1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.05 · regional, not allelic
Overall
CADD	19.61	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 0.0327% European (non-Finnish) · 385/1,176,006 alleles

Filtering AF 0.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.029%

Overall 0.0246% 393/1,597,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0327%	3,055
Remaining individualsnot grpmax-eligible	0.00646%	15,482
East Asian	0.00227%	44,100
South Asian	0.00224%	44,549
African / African-American	0.00138%	72,400

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: BRD4
Protein: p.Ile820Val
Coding: c.2458A>G
MANE Select: NM_001379291
dbSNP: rs202038315
Type: single nucleotide variant
Location: chr19:15244354 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 820: the 'disordered' region; a UniProt-annotated variant site (found in a patient with a neurodevelopmental syndrome; likely pathogenic)

Full BRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD4 p.Ile820Asn Uncertain significance ★ ⚠ same residue
BRD4 p.Ile820= Likely benign ★ same residue
BRD4 p.Tyr430Cys Likely pathogenic ★★ same type
BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same type
BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same type
BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same type
BRD4 p.Asp337Asn Uncertain significance ★★ ⚠ same type
BRD4 p.Asp497Gly 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/brd4-p-ile820val (accessed [today's date]).

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