Is BAZ2A p.Pro690Ser (c.2068C>T) pathogenic?

BAZ2A p.Pro690Ser (c.2068C>T) is classified Uncertain significance in BAZ2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0712); Very rare (popmax 0.00831%, nfe).

How common is BAZ2A p.Pro690Ser (c.2068C>T) in the general population?

BAZ2A p.Pro690Ser (c.2068C>T) is very rare (popmax 0.00831%, nfe) (gnomAD).

What do computational predictors say about BAZ2A p.Pro690Ser (c.2068C>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

BAZ2A p.Pro690Ser

c.2068C>T · VCV4645287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.20	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 1.3	GERP -0.049, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 10 kb · p 5.8e-08 · regional, not allelic
Overall
CADD	18.48	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P692S vs ClinVar P690S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00831% European (non-Finnish) · 98/1,179,852 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00657% 106/1,613,752 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,039
Remaining individualsnot grpmax-eligible	0.0064%	15,615
African / African-American	0.00267%	37,454
East Asian	0.00223%	44,898
Admixed American	0.00167%	59,994

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.Pro690Ser
Coding: c.2068C>T
MANE Select: NM_001300905
Type: single nucleotide variant
Location: chr12:56609760 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.27 · 67 PDB
Residue 690: the 'disordered' region

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

Similar variants

BAZ2A p.Ala1061Pro Uncertain significance ★ ⚠ same type
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-pro690ser (accessed [today's date]).

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