Is KAT6B p.Val1655fs (c.4962dup) pathogenic?

KAT6B p.Val1655fs (c.4962dup) is classified Pathogenic in KAT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). Associated with Inborn genetic diseases.

What condition is associated with KAT6B p.Val1655fs (c.4962dup)?

KAT6B p.Val1655fs (c.4962dup) is associated with Inborn genetic diseases (ClinVar).

KAT6B p.Val1655fs

c.4962dup · VCV4838861

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Inborn genetic diseases

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 haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (18 of 18) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: KAT6B
Protein: p.Val1655fs
Coding: c.4962dup
MANE Select: NM_012330
Type: Duplication
Location: chr10:75029785 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 3 PDB
Residue 1655: the 'interaction with runx1 and runx2' region

Full KAT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KAT6B p.Arg1577fs Pathogenic ★ same condition
KAT6B p.Glu1089fs Pathogenic ★ same condition
KAT6B p.Glu1368fs Pathogenic ★ same condition
KAT6B p.Val1655Leu Uncertain significance ★ ⚠ same residue
KAT6B p.Gln1768Ter Pathogenic ★★ same condition
KAT6B p.Lys1263fs Pathogenic ★★ same condition
KAT6B p.Ala1317Thr Uncertain significance ★★ ⚠ same condition
KAT6B p.Arg151Gln Uncertain significance ★★ ⚠ 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/kat6b-p-val1655fs (accessed [today's date]).

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