Is KAT8 p.Val94Leu (c.280G>C) pathogenic?

KAT8 p.Val94Leu (c.280G>C) is classified Uncertain significance in KAT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.2978); Absent from gnomAD v4.1.

How common is KAT8 p.Val94Leu (c.280G>C) in the general population?

KAT8 p.Val94Leu (c.280G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT8 p.Val94Leu (c.280G>C)?

AlphaMissense predicts likely benign (score 0.2978) — an in-silico prediction, not a clinical call.

KAT8 p.Val94Leu

c.280G>C · VCV3367556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2978	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 2,641 bp · p 2.7e-07 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KAT8
Protein: p.Val94Leu
Coding: c.280G>C
MANE Select: NM_032188
Type: single nucleotide variant
Location: chr16:31120254 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 44 PDB
Residue 94: the tudor-knot domain

Full KAT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KAT8 p.Tyr90Cys Likely pathogenic ★★ same type
KAT8 p.Arg144His Uncertain significance ★★ ⚠ same type
KAT8 p.Gly19Arg Uncertain significance ★★ ⚠ same type
KAT8 p.Ile57Val Uncertain significance ★★ ⚠ same type
KAT8 p.Lys203Ter Uncertain significance ★★ same type
KAT8 p.Leu370= Benign ★★ same type
KAT8 p.Pro352= Benign ★★ same type
KAT8 p.Arg108Trp Pathogenic ★ 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/kat8-p-val94leu (accessed [today's date]).

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