Is KAT6A p.Arg2003Ile (c.6008G>T) pathogenic?

KAT6A p.Arg2003Ile (c.6008G>T) is classified Uncertain significance in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely pathogenic (0.9251); Absent from gnomAD v4.1.

How common is KAT6A p.Arg2003Ile (c.6008G>T) in the general population?

KAT6A p.Arg2003Ile (c.6008G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT6A p.Arg2003Ile (c.6008G>T)?

AlphaMissense predicts likely pathogenic (score 0.9251) — an in-silico prediction, not a clinical call.

KAT6A p.Arg2003Ile

c.6008G>T · rs2486749771 · VCV2752577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9251	likely pathogenic
REVEL	0.478	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,300 bp · p 0.0013 · regional, not allelic
Overall
CADD	23.9	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: KAT6A
Protein: p.Arg2003Ile
Coding: c.6008G>T
MANE Select: NM_006766
dbSNP: rs2486749771
Type: single nucleotide variant
Location: chr8:41932212 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB

Full KAT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT6A c.3353-1G>A Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1012Ter Pathogenic ★★ same type
KAT6A p.Arg1019Ter Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg1024Ter Pathogenic ★★ same type
KAT6A p.Arg1129Ter Pathogenic ★★ same type
KAT6A p.Arg148Ter Pathogenic ★★ same type
KAT6A p.Arg220Ter Pathogenic/Likely pathogenic ★★ same type
KAT6A p.Arg251Ter Likely pathogenic ★★ 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/kat6a-p-arg2003ile (accessed [today's date]).

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