Is BRD1 p.Ala689Val (c.2066C>T) pathogenic?

BRD1 p.Ala689Val (c.2066C>T) is classified Benign in BRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-14). AlphaMissense: likely benign (0.0682); Rare (popmax 0.916%, eas).

How common is BRD1 p.Ala689Val (c.2066C>T) in the general population?

BRD1 p.Ala689Val (c.2066C>T) is rare (popmax 0.916%, eas) (gnomAD).

What do computational predictors say about BRD1 p.Ala689Val (c.2066C>T)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

BRD1 p.Ala689Val

c.2066C>T · rs145415691 · VCV717985

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.916%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.23	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 0.28	GERP -4.5
Regional constraint	o/e 0.78	unconstrained · MANE · 17 kb · p 6.5e-07 · regional, not allelic
Overall
CADD	6.461	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 0.916% East Asian · 410/44,776 alleles

Filtering AF 0.843% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.814%

Overall 0.0454% 730/1,607,434 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.916%	109
South Asian	0.151%	664
Remaining individualsnot grpmax-eligible	0.0578%	1,731
European (non-Finnish)	0.0113%	8,852
African / African-American	0.0107%	9,371
Admixed American	0.0067%	14,916
Finnishnot grpmax-eligible	0.00327%	30,541

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: BRD1
Protein: p.Ala689Val
Coding: c.2066C>T
MANE Select: NM_001304808
dbSNP: rs145415691
Type: single nucleotide variant
Location: chr22:49797837 (GRCh38)
Gene constraint: LOEUF 0.337 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.54 · 318 PDB

Full BRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD1 c.1657-4C>T Likely benign ★★ same type
BRD1 p.Ala1053= Benign ★★ same type
BRD1 p.Ala730Thr Benign ★★ same type
BRD1 p.Arg1020= Benign ★★ same type
BRD1 p.Gly620= Likely benign ★★ same type
BRD1 p.Gly776Arg Benign ★★ ⚠ same type
BRD1 p.Phe193= Benign ★★ same type
BRD1 p.Pro111= Benign ★★ 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/brd1-p-ala689val (accessed [today's date]).

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