Is BRD7 p.Pro175Ala (c.523C>G) pathogenic?

BRD7 p.Pro175Ala (c.523C>G) is classified Uncertain significance in BRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.9326); Absent from gnomAD v4.1.

How common is BRD7 p.Pro175Ala (c.523C>G) in the general population?

BRD7 p.Pro175Ala (c.523C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD7 p.Pro175Ala (c.523C>G)?

AlphaMissense predicts likely pathogenic (score 0.9326) — an in-silico prediction, not a clinical call.

BRD7 p.Pro175Ala

c.523C>G · VCV4216068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9326 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9326	likely pathogenic
REVEL	0.763	pathogenic-leaning
SaProt	LLR -10.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 20 kb · p 7.6e-08 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: BRD7
Protein: p.Pro175Ala
Coding: c.523C>G
MANE Select: NM_013263
Type: single nucleotide variant
Location: chr16:50350091 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 11 PDB
Residue 175: the bromo domain

Full BRD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD7 p.Ala101Thr Uncertain significance ★ ⚠ same type
BRD7 p.Ala284Val Uncertain significance ★ ⚠ same type
BRD7 p.Ala520Val Uncertain significance ★ ⚠ same type
BRD7 p.Ala559Thr Uncertain significance ★ ⚠ same type
BRD7 p.Arg254Gln Uncertain significance ★ ⚠ same type
BRD7 p.Arg276Ile Uncertain significance ★ ⚠ same type
BRD7 p.Arg276Lys Uncertain significance ★ ⚠ same type
BRD7 p.Arg63Pro 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/brd7-p-pro175ala (accessed [today's date]).

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