Is KAT2B p.Ser154= (c.462A>G) pathogenic?

KAT2B p.Ser154= (c.462A>G) is classified Likely benign in KAT2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-17). Very rare (popmax 0.000255%, nfe); Associated with KAT2B-related disorder.

What condition is associated with KAT2B p.Ser154= (c.462A>G)?

KAT2B p.Ser154= (c.462A>G) is associated with KAT2B-related disorder (ClinVar).

How common is KAT2B p.Ser154= (c.462A>G) in the general population?

KAT2B p.Ser154= (c.462A>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

KAT2B p.Ser154=

c.462A>G · VCV3346993

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Conditions

KAT2B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.4
Overall
CADD	3.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,178,246 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,088 alleles · very rare exomes 3/1,459,734 · genomes 0/152,354 · joint denominator

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: KAT2B
Protein: p.Ser154=
Coding: c.462A>G
MANE Select: NM_003884
Type: single nucleotide variant
Location: chr3:20095294 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.22 · 25 PDB

Full KAT2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KAT2B-related disorder

Similar variants

KAT2B p.Ile764Val Uncertain significance ★ ⚠ same condition
KAT2B p.Ala466Val Uncertain significance ⚠ same condition
KAT2B p.Gly208Ala Uncertain significance ⚠ same condition
KAT2B p.Ser434Cys Uncertain significance ⚠ same condition
KAT2B c.2157-5T>C Likely benign same condition
KAT2B c.670-3A>C Likely benign same condition
KAT2B c.852-5C>T Likely benign same condition
KAT2B p.Ala144= Likely benign same condition

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/kat2b-p-ser154 (accessed [today's date]).

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