Is KAT6A p.Arg330Cys (c.988C>T) pathogenic?

KAT6A p.Arg330Cys (c.988C>T) is classified Uncertain significance in KAT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). AlphaMissense: likely pathogenic (0.9602); Very rare (popmax 0.00333%, amr).

How common is KAT6A p.Arg330Cys (c.988C>T) in the general population?

KAT6A p.Arg330Cys (c.988C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about KAT6A p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely pathogenic (score 0.9602) — an in-silico prediction, not a clinical call.

KAT6A p.Arg330Cys

c.988C>T · rs1824194364 · VCV2789997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9602	likely pathogenic
REVEL	0.573	indeterminate
SaProt	LLR -9.60	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 8,825 bp · p 1.4e-07 · regional, not allelic
Overall
CADD	33.0	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 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,613,760 alleles · very rare exomes 6/1,461,712 · genomes 0/152,048 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
European (non-Finnish)	0.000339%	294,967

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: KAT6A
Protein: p.Arg330Cys
Coding: c.988C>T
MANE Select: NM_006766
dbSNP: rs1824194364
Type: single nucleotide variant
Location: chr8:41978697 (GRCh38)
Gene constraint: LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12 · 21 PDB
Residue 330: the 'interaction with runx1-1' region; the 'interaction with pml' region

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

Similar variants

KAT6A p.Arg330His Likely benign ★★ ⚠ same residue
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

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-arg330cys (accessed [today's date]).

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