Is KAT2B p.Ala477= (c.1431A>C) pathogenic?

KAT2B p.Ala477= (c.1431A>C) is classified Likely benign in KAT2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-21). Ultra-rare (popmax 0.0571%, sas); Associated with KAT2B-related disorder.

What condition is associated with KAT2B p.Ala477= (c.1431A>C)?

KAT2B p.Ala477= (c.1431A>C) is associated with KAT2B-related disorder (ClinVar).

How common is KAT2B p.Ala477= (c.1431A>C) in the general population?

KAT2B p.Ala477= (c.1431A>C) is ultra-rare (popmax 0.0571%, sas) (gnomAD).

KAT2B p.Ala477=

c.1431A>C · rs373721059 · VCV3055632

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, sas)

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 -0.43	GERP -1.5
Overall
CADD	4.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0571% South Asian · 52/91,050 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.00366% 59/1,613,658 alleles · ultra-rare exomes 57/1,461,516 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0571%	1,751
East Asian	0.0156%	6,413

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.Ala477=
Coding: c.1431A>C
MANE Select: NM_003884
dbSNP: rs373721059
Type: single nucleotide variant
Location: chr3:20125922 (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-ala477 (accessed [today's date]).

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