Is KAT2B p.Pro121= (c.363C>A) pathogenic?

KAT2B p.Pro121= (c.363C>A) is classified Likely benign in KAT2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Ultra-rare (popmax 0.0334%, eas); Associated with KAT2B-related disorder.

What condition is associated with KAT2B p.Pro121= (c.363C>A)?

KAT2B p.Pro121= (c.363C>A) is associated with KAT2B-related disorder (ClinVar).

How common is KAT2B p.Pro121= (c.363C>A) in the general population?

KAT2B p.Pro121= (c.363C>A) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

KAT2B p.Pro121=

c.363C>A · rs555906565 · VCV3042621

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

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 -0.89	GERP -2.7, phastCons 0.001
Overall
CADD	7.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,882 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0031% 50/1,613,416 alleles · ultra-rare exomes 42/1,461,100 · genomes 8/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
South Asian	0.0198%	5,059
Middle Eastern	0.0165%	6,062
Admixed American	0.00667%	15,003
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.000678%	147,417

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.Pro121=
Coding: c.363C>A
MANE Select: NM_003884
dbSNP: rs555906565
Type: single nucleotide variant
Location: chr3:20072392 (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.Pro121Arg Uncertain significance ★ ⚠ same residue
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

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-pro121 (accessed [today's date]).

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