Is ACAT1 p.Val359fs (c.1074_1094delinsCC) pathogenic?

ACAT1 p.Val359fs (c.10741094delinsCC) is classified Likely pathogenic in ACAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Associated with beta-ketothiolase deficiency.

What condition is associated with ACAT1 p.Val359fs (c.1074_1094delinsCC)?

ACAT1 p.Val359fs (c.1074_1094delinsCC) is associated with beta-ketothiolase deficiency (ClinVar).

How is Beta-ketothiolase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ACAT1 p.Val359fs

c.1074_1094delinsCC · VCV3775168

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

beta-ketothiolase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.77	GERP -1.9, phastCons 1

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

Variant & gene context

Gene: ACAT1
Protein: p.Val359fs
Coding: c.1074_1094delinsCC
MANE Select: NM_003101 · reported on NM_000019
Type: Indel
Location: chr11:108146270 (GRCh38)
Structure: AlphaFold pLDDT 81.22 · 5 PDB

Full ACAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

beta-ketothiolase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Beta-ketothiolase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ACAT1 p.Val359Ala Uncertain significance ★ same residue
ACAT1 p.Val359= Likely benign ★ same residue
ACAT1 p.Asn414_Gly415delinsSer Likely pathogenic ★★ same condition
ACAT1 p.Ser137fs Pathogenic/Likely pathogenic ★★ same condition
ACAT1 p.Glu255_Tyr256delinsAspAsn Uncertain significance ★★ same condition
ACAT1 c.120+374_731-68delinsTAA Pathogenic ★ same condition
ACAT1 p.Ala12fs Likely pathogenic ★ same condition
ACAT1 p.Ala215Asn Likely pathogenic ★ 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/acat1-p-val359fs (accessed [today's date]).

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