Is BRD4 p.Pro279Ser (c.835C>T) pathogenic?

BRD4 p.Pro279Ser (c.835C>T) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). AlphaMissense: likely benign (0.095); Very rare (popmax 0.00139%, afr).

How common is BRD4 p.Pro279Ser (c.835C>T) in the general population?

BRD4 p.Pro279Ser (c.835C>T) is very rare (popmax 0.00139%, afr) (gnomAD).

What do computational predictors say about BRD4 p.Pro279Ser (c.835C>T)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

BRD4 p.Pro279Ser

c.835C>T · rs1206924474 · VCV1713338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00139%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.88	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 6.3	GERP 1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 279 bp · p 0.47 · regional, not allelic
Overall
CADD	20.8	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 0.00139% African / African-American · 1/71,770 alleles

Overall 0.00132% 2/152,024 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00139%	71,770
European (non-Finnish)	8.82e-05%	1,134,050

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.Pro279Ser
Coding: c.835C>T
MANE Select: NM_001379291
dbSNP: rs1206924474
Type: single nucleotide variant
Location: chr19:15265368 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 279: 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-pro279ser (accessed [today's date]).

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