Is BRD4 p.Ile173Val (c.517A>G) pathogenic?

BRD4 p.Ile173Val (c.517A>G) is classified Conflicting classifications of pathogenicity in BRD4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-25). AlphaMissense: likely benign (0.0824); Very rare (popmax 0.00517%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BRD4 p.Ile173Val (c.517A>G)?

BRD4 p.Ile173Val (c.517A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BRD4 p.Ile173Val (c.517A>G) in the general population?

BRD4 p.Ile173Val (c.517A>G) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about BRD4 p.Ile173Val (c.517A>G)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

BRD4 p.Ile173Val

c.517A>G · rs752951417 · VCV2894061

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -2.59	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 6.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 7,296 bp · p 7.7e-17 · regional, not allelic
Overall
CADD	19.68	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 0.00517% European (non-Finnish) · 61/1,180,056 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00415% 67/1,614,130 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,470
South Asian	0.0022%	45,545

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.Ile173Val
Coding: c.517A>G
MANE Select: NM_001379291
dbSNP: rs752951417
Type: single nucleotide variant
Location: chr19:15267458 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB
Residue 173: a β-strand

Full BRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same condition
BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same condition
BRD4 p.Gln32Arg Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu715Lys Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu718Gln Uncertain significance ★★ ⚠ same condition
BRD4 p.Gly6Ala Uncertain significance ★★ ⚠ same condition

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-ile173val (accessed [today's date]).

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