Is KAT6B p.Ser504= (c.1512C>T) pathogenic?

KAT6B p.Ser504= (c.1512C>T) is classified Likely benign in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Very rare (popmax 0.00136%, nfe); Associated with genitopatellar syndrome.

What condition is associated with KAT6B p.Ser504= (c.1512C>T)?

KAT6B p.Ser504= (c.1512C>T) is associated with genitopatellar syndrome (ClinVar).

How common is KAT6B p.Ser504= (c.1512C>T) in the general population?

KAT6B p.Ser504= (c.1512C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

KAT6B p.Ser504=

c.1512C>T · VCV3727120

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

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 1.5	GERP -0.87, phastCons 1
Overall
CADD	7.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,028 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,614,004 alleles · very rare exomes 16/1,461,870 · genomes 1/152,134 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,752
African / African-American	0.00133%	74,910

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.Ser504=
Coding: c.1512C>T
MANE Select: NM_012330
Type: single nucleotide variant
Location: chr10:74975849 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 504: 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.Ser504Arg Conflicting classifications of pathogenicity ★ ⚠ 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
KAT6B p.Ala1317Thr 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-ser504 (accessed [today's date]).

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