Is KAT2A p.Ile504Val (c.1510A>G) pathogenic?

KAT2A p.Ile504Val (c.1510A>G) is classified Uncertain significance in KAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0873); Ultra-rare (popmax 0.0437%, nfe).

How common is KAT2A p.Ile504Val (c.1510A>G) in the general population?

KAT2A p.Ile504Val (c.1510A>G) is ultra-rare (popmax 0.0437%, nfe) (gnomAD).

What do computational predictors say about KAT2A p.Ile504Val (c.1510A>G)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

KAT2A p.Ile504Val

c.1510A>G · rs201214372 · VCV2358674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0437%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -0.46, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 2,980 bp · p 5.8e-17 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0437% European (non-Finnish) · 516/1,180,036 alleles

Filtering AF 0.0406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.0331% 534/1,613,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0437%	2,287
Remaining individualsnot grpmax-eligible	0.024%	4,166
African / African-American	0.00267%	37,458
South Asian	0.0011%	91,088

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.Ile504Val
Coding: c.1510A>G
MANE Select: NM_021078
dbSNP: rs201214372
Type: single nucleotide variant
Location: chr17:42117515 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.62 · 15 PDB
Residue 504: the n-acetyltransferase domain; a β-strand

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-ile504val (accessed [today's date]).

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