Is KAT7 p.Lys566Thr (c.1697A>C) pathogenic?

KAT7 p.Lys566Thr (c.1697A>C) is classified Uncertain significance in KAT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely pathogenic (0.9967); Absent from gnomAD v4.1.

How common is KAT7 p.Lys566Thr (c.1697A>C) in the general population?

KAT7 p.Lys566Thr (c.1697A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT7 p.Lys566Thr (c.1697A>C)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

KAT7 p.Lys566Thr

c.1697A>C · VCV3862489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic
REVEL	0.607	indeterminate
SaProt	LLR -11.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 1,407 bp · p 8.6e-09 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: KAT7
Protein: p.Lys566Thr
Coding: c.1697A>C
MANE Select: NM_007067
Type: single nucleotide variant
Location: chr17:49826762 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.21 · 8 PDB
Residue 566: the myst-type hat domain; a β-strand

Full KAT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT7 p.Ala449= Benign ★★ same type
KAT7 c.580+1G>A Uncertain significance ★ same type
KAT7 p.Ala133Val Uncertain significance ★ ⚠ same type
KAT7 p.Ala154Thr Uncertain significance ★ ⚠ same type
KAT7 p.Ala40Thr Uncertain significance ★ ⚠ same type
KAT7 p.Ala8Val Uncertain significance ★ ⚠ same type
KAT7 p.Arg344Leu Uncertain significance ★ ⚠ same type
KAT7 p.Arg37Gln Uncertain significance ★ ⚠ 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/kat7-p-lys566thr (accessed [today's date]).

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