Is KAT7 p.Arg75Gly (c.223A>G) pathogenic?

KAT7 p.Arg75Gly (c.223A>G) is classified Uncertain significance in KAT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.6285); Very rare (popmax 8.48e-05%, nfe).

How common is KAT7 p.Arg75Gly (c.223A>G) in the general population?

KAT7 p.Arg75Gly (c.223A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about KAT7 p.Arg75Gly (c.223A>G)?

AlphaMissense predicts likely pathogenic (score 0.6285) — an in-silico prediction, not a clinical call.

KAT7 p.Arg75Gly

c.223A>G · VCV4680689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6285	likely pathogenic
REVEL	0.138	moderately benign-leaning
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.74, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 9,676 bp · p 6e-06 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,936 alleles

Overall 6.84e-05% 1/1,461,724 alleles · very rare

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.Arg75Gly
Coding: c.223A>G
MANE Select: NM_007067
Type: single nucleotide variant
Location: chr17:49796809 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.21 · 8 PDB
Residue 75: the 'disordered' region

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-arg75gly (accessed [today's date]).

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