Is BAZ2A p.Arg669Trp (c.2005C>T) pathogenic?

BAZ2A p.Arg669Trp (c.2005C>T) is classified Uncertain significance in BAZ2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.6831); Very rare (popmax 0.00167%, amr).

How common is BAZ2A p.Arg669Trp (c.2005C>T) in the general population?

BAZ2A p.Arg669Trp (c.2005C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BAZ2A p.Arg669Trp (c.2005C>T)?

AlphaMissense predicts likely pathogenic (score 0.6831) — an in-silico prediction, not a clinical call.

BAZ2A p.Arg669Trp

c.2005C>T · VCV4645272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6831	likely pathogenic
REVEL	0.257	benign-leaning
SaProt	LLR -13.41	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 645 bp · p 3.5e-06 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R671W vs ClinVar R669W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,980 alleles

Overall 0.000248% 4/1,613,676 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,980
African / African-American	0.00134%	74,860
South Asian	0.0011%	91,058
European (non-Finnish)	8.48e-05%	1,179,839

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: BAZ2A
Protein: p.Arg669Trp
Coding: c.2005C>T
MANE Select: NM_001300905
Type: single nucleotide variant
Location: chr12:56609823 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.27 · 67 PDB
Residue 669: the 'disordered' region

Full BAZ2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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BAZ2A p.Ala1111Ser Uncertain significance ★ ⚠ same type
BAZ2A p.Ala1160Val Uncertain significance ★ ⚠ same type
BAZ2A p.Ala1223Val Uncertain significance ★ ⚠ same type
BAZ2A p.Ala1229Val Uncertain significance ★ ⚠ same type
BAZ2A p.Ala142Thr Uncertain significance ★ ⚠ same type
BAZ2A p.Ala1770Val Uncertain significance ★ ⚠ same type
BAZ2A p.Ala17Val 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/baz2a-p-arg669trp (accessed [today's date]).

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