Is BRD7 p.Ala559Thr (c.1675G>A) pathogenic?

BRD7 p.Ala559Thr (c.1675G>A) is classified Uncertain significance in BRD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.1504); Ultra-rare (popmax 0.0626%, afr).

How common is BRD7 p.Ala559Thr (c.1675G>A) in the general population?

BRD7 p.Ala559Thr (c.1675G>A) is ultra-rare (popmax 0.0626%, afr) (gnomAD).

What do computational predictors say about BRD7 p.Ala559Thr (c.1675G>A)?

AlphaMissense predicts likely benign (score 0.1504) — an in-silico prediction, not a clinical call.

BRD7 p.Ala559Thr

c.1675G>A · VCV3261729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1504 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1504	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 16 kb · p 1e-05 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.0626% African / African-American · 47/75,030 alleles

Filtering AF 0.0483% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00409% 66/1,614,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0626%	1,596
East Asian	0.0156%	6,412
Admixed American	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.000678%	147,503

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.Ala559Thr
Coding: c.1675G>A
MANE Select: NM_013263
Type: single nucleotide variant
Location: chr16:50320329 (GRCh38)
Gene constraint: LOEUF 0.336 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 11 PDB
Residue 559: an α-helix

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.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
BRD7 p.Arg84Lys 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-ala559thr (accessed [today's date]).

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