Is BAZ2A p.Glu1663Lys (c.4987G>A) pathogenic?

BAZ2A p.Glu1663Lys (c.4987G>A) is classified Uncertain significance in BAZ2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.4856); Ultra-rare (popmax 0.033%, mid).

How common is BAZ2A p.Glu1663Lys (c.4987G>A) in the general population?

BAZ2A p.Glu1663Lys (c.4987G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about BAZ2A p.Glu1663Lys (c.4987G>A)?

AlphaMissense predicts ambiguous (score 0.4856) — an in-silico prediction, not a clinical call.

BAZ2A p.Glu1663Lys

c.4987G>A · VCV4197736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4856	ambiguous
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -13.11	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 10 kb · p 5.8e-08 · regional, not allelic
Overall
CADD	25.2	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 E1665K vs ClinVar E1663K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00031% 5/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
European (non-Finnish)	0.000254%	393,301

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.Glu1663Lys
Coding: c.4987G>A
MANE Select: NM_001300905
Type: single nucleotide variant
Location: chr12:56600002 (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-glu1663lys (accessed [today's date]).

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