Is KAT8 p.Arg140Cys (c.418C>T) pathogenic?

KAT8 p.Arg140Cys (c.418C>T) is classified Pathogenic in KAT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KAT8 p.Arg140Cys (c.418C>T)?

KAT8 p.Arg140Cys (c.418C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KAT8 p.Arg140Cys (c.418C>T) in the general population?

KAT8 p.Arg140Cys (c.418C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KAT8 p.Arg140Cys (c.418C>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

KAT8 p.Arg140Cys

c.418C>T · rs2544163778 · VCV2217472

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar
REVEL	0.387	indeterminate
SaProt	LLR -14.24	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 6,748 bp · p 8.6e-11 · regional, not allelic
Overall
CADD	32.0	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

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.Arg140Cys
Coding: c.418C>T
MANE Select: NM_032188
dbSNP: rs2544163778
Type: single nucleotide variant
Location: chr16:31120470 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 44 PDB

Full KAT8 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

KAT8 p.Tyr90Cys Likely pathogenic ★★ same condition
KAT8 p.Arg144His Uncertain significance ★★ ⚠ same condition
KAT8 c.1312+12G>A Uncertain significance ★ same condition
KAT8 c.1312+16C>G Uncertain significance ★ same condition
KAT8 c.1312+25G>C Uncertain significance ★ same condition
KAT8 c.1312+31G>A Uncertain significance ★ same condition
KAT8 c.1312+58G>A Uncertain significance ★ same condition
KAT8 c.1312+82C>G 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/kat8-p-arg140cys (accessed [today's date]).

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