Is BRD3 p.Pro194Ser (c.580C>T) pathogenic?

BRD3 p.Pro194Ser (c.580C>T) is classified Uncertain significance in BRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.2057); Ultra-rare (popmax 0.0664%, mid).

How common is BRD3 p.Pro194Ser (c.580C>T) in the general population?

BRD3 p.Pro194Ser (c.580C>T) is ultra-rare (popmax 0.0664%, mid) (gnomAD).

What do computational predictors say about BRD3 p.Pro194Ser (c.580C>T)?

AlphaMissense predicts likely benign (score 0.2057) — an in-silico prediction, not a clinical call.

BRD3 p.Pro194Ser

c.580C>T · VCV3261712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0664%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2057	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,222 bp · p 0.8 · regional, not allelic
Overall
CADD	24.6	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 0.0664% Middle Eastern · 4/6,022 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00212% 34/1,607,096 alleles · ultra-rare exomes 30/1,454,936 · genomes 4/152,160 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0664%	1,506
Remaining individualsnot grpmax-eligible	0.00803%	12,446
South Asian	0.00553%	18,078
European (non-Finnish)	0.0017%	58,829

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: BRD3
Protein: p.Pro194Ser
Coding: c.580C>T
MANE Select: NM_007371
Type: single nucleotide variant
Location: chr9:134050508 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.65 · 48 PDB

Full BRD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD3 p.Thr15= Benign ★★ same type
BRD3 c.1407+5G>A Uncertain significance ★ same type
BRD3 p.Ala10Val Uncertain significance ★ ⚠ same type
BRD3 p.Ala14Val Uncertain significance ★ ⚠ same type
BRD3 p.Ala161Val Uncertain significance ★ ⚠ same type
BRD3 p.Ala173Thr Uncertain significance ★ ⚠ same type
BRD3 p.Ala173Val Uncertain significance ★ ⚠ same type
BRD3 p.Ala198Val 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/brd3-p-pro194ser (accessed [today's date]).

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