Is BRD8 p.Ala559Thr (c.1675G>A) pathogenic?

BRD8 p.Ala559Thr (c.1675G>A) is classified Uncertain significance in BRD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely benign (0.0597); Absent from gnomAD v4.1.

How common is BRD8 p.Ala559Thr (c.1675G>A) in the general population?

BRD8 p.Ala559Thr (c.1675G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRD8 p.Ala559Thr (c.1675G>A)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

BRD8 p.Ala559Thr

c.1675G>A · VCV3482325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.39	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 -0.46	GERP -0.15, phastCons 0.01
Regional constraint	o/e 1.00	unconstrained · MANE · 647 bp · p 1 · regional, not allelic
Overall
CADD	14.03	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

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: BRD8
Protein: p.Ala559Thr
Coding: c.1675G>A
MANE Select: NM_139199
Type: single nucleotide variant
Location: chr5:138164770 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.92
Residue 559: the 'disordered' region

Full BRD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD8 p.Ala165Val Uncertain significance ★ ⚠ same type
BRD8 p.Ala211Thr Uncertain significance ★ ⚠ same type
BRD8 p.Ala264Val Uncertain significance ★ ⚠ same type
BRD8 p.Ala273Ser Uncertain significance ★ ⚠ same type
BRD8 p.Ala314Val Uncertain significance ★ ⚠ same type
BRD8 p.Ala331Thr Uncertain significance ★ ⚠ same type
BRD8 p.Ala437Thr Uncertain significance ★ ⚠ same type
BRD8 p.Ala553Val 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/brd8-p-ala559thr (accessed [today's date]).

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