Is KAT2A p.Arg338Gln (c.1013G>A) pathogenic?

KAT2A p.Arg338Gln (c.1013G>A) is classified Uncertain significance in KAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-25). AlphaMissense: likely pathogenic (0.8848); Very rare (popmax 0.00223%, eas).

How common is KAT2A p.Arg338Gln (c.1013G>A) in the general population?

KAT2A p.Arg338Gln (c.1013G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about KAT2A p.Arg338Gln (c.1013G>A)?

AlphaMissense predicts likely pathogenic (score 0.8848) — an in-silico prediction, not a clinical call.

KAT2A p.Arg338Gln

c.1013G>A · VCV4680669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8848	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -13.40	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,776 bp · p 9e-13 · regional, not allelic
Overall
CADD	28.6	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,082 alleles · very rare exomes 4/1,461,744 · genomes 0/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
African / African-American	0.00133%	75,054
European (non-Finnish)	0.000169%	589,977

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: KAT2A
Protein: p.Arg338Gln
Coding: c.1013G>A
MANE Select: NM_021078
Type: single nucleotide variant
Location: chr17:42119305 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.62 · 15 PDB

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-arg338gln (accessed [today's date]).

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