Is BAZ2A p.Leu31Pro (c.92T>C) pathogenic?

BAZ2A p.Leu31Pro (c.92T>C) is classified Uncertain significance in BAZ2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: ambiguous (0.5032); Ultra-rare (popmax 0.0286%, nfe).

How common is BAZ2A p.Leu31Pro (c.92T>C) in the general population?

BAZ2A p.Leu31Pro (c.92T>C) is ultra-rare (popmax 0.0286%, nfe) (gnomAD).

What do computational predictors say about BAZ2A p.Leu31Pro (c.92T>C)?

AlphaMissense predicts ambiguous (score 0.5032) — an in-silico prediction, not a clinical call.

BAZ2A p.Leu31Pro

c.92T>C · rs369661356 · VCV2374695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5032 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5032	ambiguous
REVEL	0.187	benign-leaning
SaProt	LLR -7.03	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.76, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,062 bp · p 0.042 · regional, not allelic
Overall
CADD	22.7	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 L33P vs ClinVar L31P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0286% European (non-Finnish) · 336/1,176,552 alleles

Filtering AF 0.026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.0215% 346/1,606,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0286%	3,502
Remaining individualsnot grpmax-eligible	0.00964%	10,372
African / African-American	0.00535%	18,683

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.Leu31Pro
Coding: c.92T>C
MANE Select: NM_001300905
dbSNP: rs369661356
Type: single nucleotide variant
Location: chr12:56617439 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.27 · 67 PDB
Residue 31: 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-leu31pro (accessed [today's date]).

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