Is BAZ1A p.Pro515Ala (c.1543C>G) pathogenic?

BAZ1A p.Pro515Ala (c.1543C>G) is classified Uncertain significance in BAZ1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.2353); Ultra-rare (popmax 0.0107%, afr).

How common is BAZ1A p.Pro515Ala (c.1543C>G) in the general population?

BAZ1A p.Pro515Ala (c.1543C>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about BAZ1A p.Pro515Ala (c.1543C>G)?

AlphaMissense predicts likely benign (score 0.2353) — an in-silico prediction, not a clinical call.

BAZ1A p.Pro515Ala

c.1543C>G · rs756557984 · VCV2306145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2353 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2353	likely benign
REVEL	0.135	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 8.7	GERP 2, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 17 kb · p 1.1e-19 · 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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,814 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000558% 9/1,613,450 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,352
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: BAZ1A
Protein: p.Pro515Ala
Coding: c.1543C>G
MANE Select: NM_013448
dbSNP: rs756557984
Type: single nucleotide variant
Location: chr14:34786189 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.97 · 1 PDB

Full BAZ1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAZ1A p.Arg876Cys Benign ★★ same type
BAZ1A p.Leu1017= Benign ★★ same type
BAZ1A c.1511-1G>T Uncertain significance ★ same type
BAZ1A p.Ala1551Val Uncertain significance ★ ⚠ same type
BAZ1A p.Ala272Val Uncertain significance ★ ⚠ same type
BAZ1A p.Ala298Gly Uncertain significance ★ ⚠ same type
BAZ1A p.Ala304Thr Uncertain significance ★ ⚠ same type
BAZ1A p.Ala337Val 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/baz1a-p-pro515ala (accessed [today's date]).

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