Is BRD3 p.Arg607Lys (c.1820G>A) pathogenic?

BRD3 p.Arg607Lys (c.1820G>A) is classified Uncertain significance in BRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: ambiguous (0.4241); Absent from gnomAD v4.1.

How common is BRD3 p.Arg607Lys (c.1820G>A) in the general population?

BRD3 p.Arg607Lys (c.1820G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD3 p.Arg607Lys (c.1820G>A)?

AlphaMissense predicts ambiguous (score 0.4241) — an in-silico prediction, not a clinical call.

BRD3 p.Arg607Lys

c.1820G>A · VCV3482289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4241 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4241	ambiguous
REVEL	0.056	moderately benign-leaning
SaProt	LLR -4.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP 1.9, phastCons 0.25
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 9.2e-15 · regional, not allelic
Overall
CADD	23.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRD3
Protein: p.Arg607Lys
Coding: c.1820G>A
MANE Select: NM_007371
Type: single nucleotide variant
Location: chr9:134036148 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.65 · 48 PDB
Residue 607: the net domain; an α-helix

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-arg607lys (accessed [today's date]).

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