Is KAT6A p.Pro565Arg (c.1694C>G) pathogenic?

KAT6A p.Pro565Arg (c.1694C>G) is classified Likely pathogenic in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.9981); Absent from gnomAD v4.1; Associated with autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome.

How common is KAT6A p.Pro565Arg (c.1694C>G) in the general population?

KAT6A p.Pro565Arg (c.1694C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6A p.Pro565Arg (c.1694C>G)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

KAT6A p.Pro565Arg

Q: What condition is associated with KAT6A p.Pro565Arg (c.1694C>G)?

KAT6A p.Pro565Arg (c.1694C>G) is associated with autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (ClinVar).

c.1694C>G · VCV4851431

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic ✓ concordant with ClinVar · top 3% in KAT6A
REVEL	0.705	pathogenic-leaning
SaProt	LLR -18.84	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	27.6	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.Pro565Arg
Coding: c.1694C>G
MANE Select: NM_006766
Type: single nucleotide variant
Location: chr8:41949268 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 565: 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

autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6A p.Arg1012Ter Pathogenic ★★ same condition
KAT6A p.Arg1019Ter Pathogenic/Likely pathogenic ★★ same condition
KAT6A p.Arg1024Ter Pathogenic ★★ same condition
KAT6A p.Arg1129Ter Pathogenic ★★ same condition
KAT6A p.Arg220Ter Pathogenic/Likely pathogenic ★★ same condition
KAT6A p.Arg251Ter Likely pathogenic ★★ same condition
KAT6A p.Arg269Ter Pathogenic ★★ same condition
KAT6A p.Arg286Ter Pathogenic ★★ 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/kat6a-p-pro565arg (accessed [today's date]).

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