Is BRD4 p.Glu1270Asp (c.3810G>C) pathogenic?

BRD4 p.Glu1270Asp (c.3810G>C) is classified Likely benign in BRD4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.3249); Rare (popmax 0.839%, nfe).

How common is BRD4 p.Glu1270Asp (c.3810G>C) in the general population?

BRD4 p.Glu1270Asp (c.3810G>C) is rare (popmax 0.839%, nfe) (gnomAD).

What do computational predictors say about BRD4 p.Glu1270Asp (c.3810G>C)?

AlphaMissense predicts likely benign (score 0.3249) — an in-silico prediction, not a clinical call.

BRD4 p.Glu1270Asp

c.3810G>C · rs113881069 · VCV775116

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.3249 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.839%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3249	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.59	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 0.34	GERP -2.5, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 321 bp · p 0.41 · regional, not allelic
Overall
CADD	18.76	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 0.839% European (non-Finnish) · 9,842/1,173,122 alleles

Filtering AF 0.825% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.819%

Overall 0.691% 11,029/1,595,662 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.839%	119
Remaining individualsnot grpmax-eligible	0.743%	135
Ashkenazi Jewishnot grpmax-eligible	0.423%	236
Admixed American	0.358%	279
Finnishnot grpmax-eligible	0.338%	296
Middle Eastern	0.15%	666
African / African-American	0.148%	673
South Asian	0.0903%	1,108

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.Glu1270Asp
Coding: c.3810G>C
MANE Select: NM_001379291
dbSNP: rs113881069
Type: single nucleotide variant
Location: chr19:15238953 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 1270: the 'c-terminal (ctd) region' region; 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.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
BRD4 p.Gln32Arg Uncertain significance ★★ ⚠ same type
BRD4 p.Glu1123Lys 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-glu1270asp (accessed [today's date]).

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