Is KAT6B p.Ser522= (c.1566T>C) pathogenic?

KAT6B p.Ser522= (c.1566T>C) is classified Likely benign in KAT6B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-13). Ultra-rare (popmax 0.0245%, eas); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Ser522= (c.1566T>C)?

KAT6B p.Ser522= (c.1566T>C) is associated with genitopatellar syndrome (ClinVar).

How common is KAT6B p.Ser522= (c.1566T>C) in the general population?

KAT6B p.Ser522= (c.1566T>C) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

KAT6B p.Ser522=

c.1566T>C · rs540521199 · VCV1558230

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

genitopatellar syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.051	GERP -1, phastCons 0.96
Overall
CADD	4.412	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,878 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000743% 12/1,614,152 alleles · ultra-rare exomes 10/1,461,874 · genomes 2/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
European (non-Finnish)	8.47e-05%	1,180,025

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: KAT6B
Protein: p.Ser522=
Coding: c.1566T>C
MANE Select: NM_012330
dbSNP: rs540521199
Type: single nucleotide variant
Location: chr10:74975903 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 522: the 'disordered' region; the 'negatively regulates hat activity' region

Full KAT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

genitopatellar syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6B p.Ser522Tyr Likely benign ★ ⚠ same residue
KAT6B p.Ser522Cys Uncertain significance ★ ⚠ same residue
KAT6B c.3664+1G>A Pathogenic ★★ same condition
KAT6B p.Arg1058Ter Pathogenic ★★ same condition
KAT6B p.Arg1797Ter Pathogenic ★★ same condition
KAT6B p.Gln1752Ter Pathogenic ★★ same condition
KAT6B c.2373+6C>A Uncertain significance ★★ same condition
KAT6B c.2374-3T>C Uncertain significance ★★ same condition

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/kat6b-p-ser522 (accessed [today's date]).

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