Is KAT2B p.Pro725fs (c.2174del) pathogenic?

KAT2B p.Pro725fs (c.2174del) is classified Uncertain significance in KAT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-11). Very rare (popmax 8.48e-05%, nfe).

How common is KAT2B p.Pro725fs (c.2174del) in the general population?

KAT2B p.Pro725fs (c.2174del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

KAT2B p.Pro725fs

c.2174del · VCV4961488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 16 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,882 alleles

Overall 6.2e-05% 1/1,613,986 alleles · very rare exomes 1/1,461,714 · genomes 0/152,272 · 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.Pro725fs
Coding: c.2174del
MANE Select: NM_003884
Type: Deletion
Location: chr3:20148258 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.22 · 25 PDB
Residue 725: the bromo domain; the 'disordered' region

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

Similar variants

KAT2B p.Pro725= Likely benign same residue
KAT2B p.Ala88fs Uncertain significance ★ same type
KAT2B p.Asn361fs Uncertain significance ★ same type
KAT2B p.Tyr585fs Uncertain significance ★ same type
KAT2B p.Ala14_Gly53del Likely benign 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/kat2b-p-pro725fs (accessed [today's date]).

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