Is BAZ2A p.Lys565Arg (c.1694A>G) pathogenic?

BAZ2A p.Lys565Arg (c.1694A>G) is classified Uncertain significance in BAZ2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0855); Ultra-rare (popmax 0.0164%, mid).

How common is BAZ2A p.Lys565Arg (c.1694A>G) in the general population?

BAZ2A p.Lys565Arg (c.1694A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BAZ2A p.Lys565Arg (c.1694A>G)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

BAZ2A p.Lys565Arg

c.1694A>G · rs759675179 · VCV2346036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,062 bp · p 0.042 · regional, not allelic
Overall
CADD	22.4	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 K567R vs ClinVar K565R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00322% 52/1,612,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.00801%	12,488
South Asian	0.00551%	18,164
African / African-American	0.00401%	24,965
European (non-Finnish)	0.00322%	31,041

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.Lys565Arg
Coding: c.1694A>G
MANE Select: NM_001300905
dbSNP: rs759675179
Type: single nucleotide variant
Location: chr12:56610494 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.27 · 67 PDB
Residue 565: the mbd domain; a β-strand

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

Similar variants

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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
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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-lys565arg (accessed [today's date]).

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