Is KAT6A p.Pro528Ser (c.1582C>T) pathogenic?

KAT6A p.Pro528Ser (c.1582C>T) is classified Likely pathogenic in KAT6A (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9863); Absent from gnomAD v4.1; Associated with autism spectrum disorder.

What condition is associated with KAT6A p.Pro528Ser (c.1582C>T)?

KAT6A p.Pro528Ser (c.1582C>T) is associated with autism spectrum disorder (ClinVar).

How common is KAT6A p.Pro528Ser (c.1582C>T) in the general population?

KAT6A p.Pro528Ser (c.1582C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6A p.Pro528Ser (c.1582C>T)?

AlphaMissense predicts likely pathogenic (score 0.9863) — an in-silico prediction, not a clinical call.

KAT6A p.Pro528Ser

c.1582C>T · rs1822869930 · VCV996682

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9863 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autism spectrum disorder

Computational evidence

Protein change
AlphaMissense	0.9863	likely pathogenic ✓ concordant with ClinVar · top 10% in KAT6A
REVEL	0.752	pathogenic-leaning
SaProt	LLR -12.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 7,470 bp · p 7.1e-06 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KAT6A
Protein: p.Pro528Ser
Coding: c.1582C>T
MANE Select: NM_006766
dbSNP: rs1822869930
Type: single nucleotide variant
Location: chr8:41955312 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 528: the 'interaction with runx1-1' region; the 'catalytic' region; the 'mediates interaction with brpf1, required for histone h3 acetyltransferase activity' region; the myst-type hat domain; the 'interaction with pml' region

Full KAT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6A p.Glu1221Lys Likely benign ★★ same condition
KAT6A p.Ser1558Arg Likely pathogenic ★ ⚠ same condition
KAT6A c.3353-1G>A Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1012Ter Pathogenic ★★ same type
KAT6A p.Arg1019Ter Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1024Ter Pathogenic ★★ same type
KAT6A p.Arg1129Ter Pathogenic ★★ same type
KAT6A p.Arg148Ter Pathogenic ★★ 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/kat6a-p-pro528ser (accessed [today's date]).

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