Is BRD3 p.Ala14Val (c.41C>T) pathogenic?

BRD3 p.Ala14Val (c.41C>T) is classified Uncertain significance in BRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0692); Very rare (popmax 0.00267%, afr).

How common is BRD3 p.Ala14Val (c.41C>T) in the general population?

BRD3 p.Ala14Val (c.41C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BRD3 p.Ala14Val (c.41C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

BRD3 p.Ala14Val

c.41C>T · VCV4828013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.79	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 0.35	GERP -2.4, phastCons 0.003
Regional constraint	o/e 1.13	unconstrained · MANE · 80 bp · p 0.4 · regional, not allelic
Overall
CADD	15.95	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 0.00267% African / African-American · 2/75,004 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000683% 11/1,610,192 alleles · very rare exomes 9/1,457,942 · genomes 2/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,502
Admixed American	0.00167%	59,926
Finnishnot grpmax-eligible	0.00163%	61,308
South Asian	0.0011%	91,020
European (non-Finnish)	0.000509%	196,563

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.Ala14Val
Coding: c.41C>T
MANE Select: NM_007371
Type: single nucleotide variant
Location: chr9:134053437 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.65 · 48 PDB
Residue 14: the 'disordered' region

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.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
BRD3 p.Ala206Thr 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-ala14val (accessed [today's date]).

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