Is KAT2A p.Pro153Leu (c.458C>T) pathogenic?

KAT2A p.Pro153Leu (c.458C>T) is classified Likely benign in KAT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-28). AlphaMissense: likely benign (0.085); Rare (popmax 0.227%, amr).

How common is KAT2A p.Pro153Leu (c.458C>T) in the general population?

KAT2A p.Pro153Leu (c.458C>T) is rare (popmax 0.227%, amr) (gnomAD).

What do computational predictors say about KAT2A p.Pro153Leu (c.458C>T)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

KAT2A p.Pro153Leu

c.458C>T · rs782241423 · VCV745850

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -9.11	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,776 bp · p 9e-13 · regional, not allelic
Overall
CADD	25.3	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 0.227% Admixed American · 136/59,994 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.00917% 148/1,613,896 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.227%	441
Remaining individualsnot grpmax-eligible	0.016%	6,248
European (non-Finnish)	0.000169%	590,016

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.Pro153Leu
Coding: c.458C>T
MANE Select: NM_021078
dbSNP: rs782241423
Type: single nucleotide variant
Location: chr17:42120711 (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-pro153leu (accessed [today's date]).

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