Is KAT2A p.Lys623Arg (c.1868A>G) pathogenic?

KAT2A p.Lys623Arg (c.1868A>G) is classified Uncertain significance in KAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.2082); Absent from gnomAD v4.1.

How common is KAT2A p.Lys623Arg (c.1868A>G) in the general population?

KAT2A p.Lys623Arg (c.1868A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT2A p.Lys623Arg (c.1868A>G)?

AlphaMissense predicts likely benign (score 0.2082) — an in-silico prediction, not a clinical call.

KAT2A p.Lys623Arg

c.1868A>G · VCV4089756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2082	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 2,980 bp · p 5.8e-17 · regional, not allelic
Overall
CADD	26.9	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: KAT2A
Protein: p.Lys623Arg
Coding: c.1868A>G
MANE Select: NM_021078
Type: single nucleotide variant
Location: chr17:42115730 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.62 · 15 PDB
Residue 623: the n-acetyltransferase domain; an α-helix

Full KAT2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT2A c.464-18C>G Benign ★★ same type
KAT2A p.Leu664= Benign ★★ same type
KAT2A p.Leu719= Benign ★★ same type
KAT2A p.Ala274Val Uncertain significance ★ ⚠ same type
KAT2A p.Ala426Val Uncertain significance ★ ⚠ same type
KAT2A p.Ala53Ser Uncertain significance ★ ⚠ same type
KAT2A p.Ala53Val Uncertain significance ★ ⚠ same type
KAT2A p.Arg171Gly 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/kat2a-p-lys623arg (accessed [today's date]).

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