Is KAT7 p.Lys537Gln (c.1609A>C) pathogenic?

KAT7 p.Lys537Gln (c.1609A>C) is classified Uncertain significance in KAT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.3344); Ultra-rare (popmax 0.0223%, eas).

How common is KAT7 p.Lys537Gln (c.1609A>C) in the general population?

KAT7 p.Lys537Gln (c.1609A>C) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about KAT7 p.Lys537Gln (c.1609A>C)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

KAT7 p.Lys537Gln

c.1609A>C · rs756110504 · VCV3112776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; 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	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0223% East Asian · 10/44,892 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00062% 10/1,613,914 alleles · ultra-rare exomes 8/1,461,666 · genomes 2/152,248 · joint denominator

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: KAT7
Protein: p.Lys537Gln
Coding: c.1609A>C
MANE Select: NM_007067
dbSNP: rs756110504
Type: single nucleotide variant
Location: chr17:49826128 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.21 · 8 PDB
Residue 537: 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.Lys537Glu Uncertain significance ★ ⚠ same residue
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

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-lys537gln (accessed [today's date]).

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