Is BRD7 p.Pro622Leu (c.1865C>T) pathogenic?

BRD7 p.Pro622Leu (c.1865C>T) is classified Uncertain significance in BRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.0679); Ultra-rare (popmax 0.012%, afr).

How common is BRD7 p.Pro622Leu (c.1865C>T) in the general population?

BRD7 p.Pro622Leu (c.1865C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about BRD7 p.Pro622Leu (c.1865C>T)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

BRD7 p.Pro622Leu

c.1865C>T · VCV3482302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.71	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 5.7	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 16 kb · p 1e-05 · regional, not allelic
Overall
CADD	19.2	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 0.012% African / African-American · 9/74,862 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00112% 18/1,612,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,318
Remaining individualsnot grpmax-eligible	0.0016%	62,324
European (non-Finnish)	0.000678%	147,493

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: BRD7
Protein: p.Pro622Leu
Coding: c.1865C>T
MANE Select: NM_013263
Type: single nucleotide variant
Location: chr16:50319922 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 11 PDB

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-pro622leu (accessed [today's date]).

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