Is BRD4 p.Thr1006Pro (c.3016A>C) pathogenic?

BRD4 p.Thr1006Pro (c.3016A>C) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-31). AlphaMissense: likely benign (0.049); Very rare (popmax 0.00479%, afr).

How common is BRD4 p.Thr1006Pro (c.3016A>C) in the general population?

BRD4 p.Thr1006Pro (c.3016A>C) is very rare (popmax 0.00479%, afr) (gnomAD).

What do computational predictors say about BRD4 p.Thr1006Pro (c.3016A>C)?

AlphaMissense predicts likely benign (score 0.049) — an in-silico prediction, not a clinical call.

BRD4 p.Thr1006Pro

c.3016A>C · VCV3685152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00479%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.049	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -3.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Pangolin	Δ0.28	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -2.6	GERP -1.6
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.05 · regional, not allelic
Overall
CADD	13.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00479% African / African-American · 3/62,650 alleles

Filtering AF 0.00127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000652%

Overall 0.000868% 13/1,498,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00479%	20,883
South Asian	0.0037%	27,041
East Asian	0.00256%	39,072
European (non-Finnish)	0.000533%	187,771

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.Thr1006Pro
Coding: c.3016A>C
MANE Select: NM_001379291
Type: single nucleotide variant
Location: chr19:15243053 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 1006: 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-thr1006pro (accessed [today's date]).

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