Is KAT8 p.Arg108Trp (c.322C>T) pathogenic?

KAT8 p.Arg108Trp (c.322C>T) is classified Pathogenic in KAT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.9797); Very rare (popmax 8.48e-05%, nfe).

How common is KAT8 p.Arg108Trp (c.322C>T) in the general population?

KAT8 p.Arg108Trp (c.322C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about KAT8 p.Arg108Trp (c.322C>T)?

AlphaMissense predicts likely pathogenic (score 0.9797) — an in-silico prediction, not a clinical call.

KAT8 p.Arg108Trp

c.322C>T · VCV3343475

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9797 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9797	likely pathogenic ✓ concordant with ClinVar
REVEL	0.491	indeterminate
SaProt	LLR -16.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	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	29.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,886 alleles

Overall 6.84e-05% 1/1,461,686 alleles · very rare

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: KAT8
Protein: p.Arg108Trp
Coding: c.322C>T
MANE Select: NM_032188
Type: single nucleotide variant
Location: chr16:31120374 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 44 PDB
Residue 108: 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.Arg140Cys 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-arg108trp (accessed [today's date]).

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