Is BRD4 p.Ile820= (c.2460C>T) pathogenic?

BRD4 p.Ile820= (c.2460C>T) is classified Likely benign in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Very rare (popmax 0.009%, eas).

How common is BRD4 p.Ile820= (c.2460C>T) in the general population?

BRD4 p.Ile820= (c.2460C>T) is very rare (popmax 0.009%, eas) (gnomAD).

BRD4 p.Ile820=

c.2460C>T · VCV4779744

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.009%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -2.1
Overall
CADD	6.836	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.009% East Asian · 4/44,454 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.0011% 16/1,452,144 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.009%	11,113
South Asian	0.00448%	22,308
Admixed American	0.0017%	58,750
Remaining individualsnot grpmax-eligible	0.00161%	62,116
European (non-Finnish)	0.00051%	196,244

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.Ile820=
Coding: c.2460C>T
MANE Select: NM_001379291
Type: single nucleotide variant
Location: chr19:15244352 (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.Ile820Val Conflicting classifications of pathogenicity ★ ⚠ 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-ile820 (accessed [today's date]).

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