Is BAZ2A p.Pro1252Ala (c.3754C>G) pathogenic?

BAZ2A p.Pro1252Ala (c.3754C>G) is classified Uncertain significance in BAZ2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0797); Ultra-rare (popmax 0.032%, nfe).

How common is BAZ2A p.Pro1252Ala (c.3754C>G) in the general population?

BAZ2A p.Pro1252Ala (c.3754C>G) is ultra-rare (popmax 0.032%, nfe) (gnomAD).

What do computational predictors say about BAZ2A p.Pro1252Ala (c.3754C>G)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

BAZ2A p.Pro1252Ala

c.3754C>G · rs199886609 · VCV2408131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.36	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 6.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 10 kb · p 5.8e-08 · regional, not allelic
Overall
CADD	20.8	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 P1254A vs ClinVar P1252A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% European (non-Finnish) · 377/1,179,864 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0282%

Overall 0.0253% 408/1,613,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.032%	3,130
Remaining individualsnot grpmax-eligible	0.0272%	3,676
Admixed American	0.01%	10,001
South Asian	0.00659%	15,181
Finnishnot grpmax-eligible	0.00156%	64,008
African / African-American	0.00133%	75,034

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.Pro1252Ala
Coding: c.3754C>G
MANE Select: NM_001300905
dbSNP: rs199886609
Type: single nucleotide variant
Location: chr12:56601863 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.27 · 67 PDB

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-pro1252ala (accessed [today's date]).

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