Is BRD4 p.Ala1248Val (c.3743C>T) pathogenic?

BRD4 p.Ala1248Val (c.3743C>T) is classified Benign/Likely benign in BRD4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0894); Ultra-rare (popmax 0.0193%, nfe).

How common is BRD4 p.Ala1248Val (c.3743C>T) in the general population?

BRD4 p.Ala1248Val (c.3743C>T) is ultra-rare (popmax 0.0193%, nfe) (gnomAD).

What do computational predictors say about BRD4 p.Ala1248Val (c.3743C>T)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

BRD4 p.Ala1248Val

c.3743C>T · rs141774763 · VCV2155841

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 321 bp · p 0.41 · regional, not allelic
Overall
CADD	23.0	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 0.0193% European (non-Finnish) · 228/1,179,282 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0164%

Overall 0.0955% 1,534/1,606,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.13%	47
Remaining individualsnot grpmax-eligible	0.104%	959
European (non-Finnish)grpmax	0.0193%	5,172
African / African-American	0.00133%	74,980

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala1248Val
Coding: c.3743C>T
MANE Select: NM_001379291
dbSNP: rs141774763
Type: single nucleotide variant
Location: chr19:15239098 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 1248: 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-ala1248val (accessed [today's date]).

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