Is KAT7 p.Ile544Met (c.1632C>G) pathogenic?

KAT7 p.Ile544Met (c.1632C>G) is classified Uncertain significance in KAT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: ambiguous (0.3601); Very rare (popmax 0.00365%, nfe).

How common is KAT7 p.Ile544Met (c.1632C>G) in the general population?

KAT7 p.Ile544Met (c.1632C>G) is very rare (popmax 0.00365%, nfe) (gnomAD).

What do computational predictors say about KAT7 p.Ile544Met (c.1632C>G)?

AlphaMissense predicts ambiguous (score 0.3601) — an in-silico prediction, not a clinical call.

KAT7 p.Ile544Met

c.1632C>G · VCV4089820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00365%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3601	ambiguous
REVEL	0.316	indeterminate
SaProt	LLR -6.90	tolerated
Splicing
SpliceAI	Δ0.30	acceptor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.011	GERP -2.9, phastCons 0.92
Regional constraint	o/e 0.43	unconstrained · MANE · 1,407 bp · p 8.6e-09 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.00365% European (non-Finnish) · 43/1,177,628 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00273% 44/1,609,290 alleles · very rare exomes 42/1,457,096 · genomes 2/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00365%	27,387
Remaining individualsnot grpmax-eligible	0.00161%	62,226

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.Ile544Met
Coding: c.1632C>G
MANE Select: NM_007067
Type: single nucleotide variant
Location: chr17:49826697 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.21 · 8 PDB
Residue 544: the myst-type hat domain; an α-helix

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-ile544met (accessed [today's date]).

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