Is BRD4 p.Phe1227= (c.3681C>T) pathogenic?

BRD4 p.Phe1227= (c.3681C>T) is classified Benign/Likely benign in BRD4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). Rare (popmax 0.521%, nfe).

How common is BRD4 p.Phe1227= (c.3681C>T) in the general population?

BRD4 p.Phe1227= (c.3681C>T) is rare (popmax 0.521%, nfe) (gnomAD).

BRD4 p.Phe1227=

c.3681C>T · rs148010154 · VCV787604

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.521%, nfe)

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 2.5	GERP -2.7, phastCons 1
Overall
CADD	4.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.521% European (non-Finnish) · 6,144/1,179,982 alleles

Filtering AF 0.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.505%

Overall 0.439% 7,078/1,612,748 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.596%	168
European (non-Finnish)grpmax	0.521%	192
Remaining individualsnot grpmax-eligible	0.4%	250
Ashkenazi Jewishnot grpmax-eligible	0.345%	290
Admixed American	0.173%	577
Middle Eastern	0.066%	1,516
South Asian	0.0637%	1,570
African / African-American	0.0559%	1,787

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.Phe1227=
Coding: c.3681C>T
MANE Select: NM_001379291
dbSNP: rs148010154
Type: single nucleotide variant
Location: chr19:15239160 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 1227: 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-phe1227 (accessed [today's date]).

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