Is ACAT1 p.Ala348= (c.1044A>C) pathogenic?

ACAT1 p.Ala348= (c.1044A>C) is classified Likely benign in ACAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Very rare (popmax 0.000424%, nfe); Associated with beta-ketothiolase deficiency.

What condition is associated with ACAT1 p.Ala348= (c.1044A>C)?

ACAT1 p.Ala348= (c.1044A>C) is associated with beta-ketothiolase deficiency (ClinVar).

How common is ACAT1 p.Ala348= (c.1044A>C) in the general population?

ACAT1 p.Ala348= (c.1044A>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Beta-ketothiolase deficiency inherited?

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

ACAT1 p.Ala348=

c.1044A>C · rs2134791187 · VCV1535429

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

beta-ketothiolase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.35	GERP -5.3, phastCons 0.001
Overall
CADD	6.914	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,554 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,204 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: ACAT1
Protein: p.Ala348=
Coding: c.1044A>C
MANE Select: NM_003101 · reported on NM_000019
dbSNP: rs2134791187
Type: single nucleotide variant
Location: chr11:108146240 (GRCh38)
Structure: AlphaFold pLDDT 81.22 · 5 PDB
Residue 348: an α-helix

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.Ala348fs Likely pathogenic same residue
ACAT1 c.1006-1G>A Pathogenic ★★ same condition
ACAT1 c.1006-1G>C Pathogenic ★★ same condition
ACAT1 c.1006-2A>C Pathogenic ★★ same condition
ACAT1 c.1163+2T>C Pathogenic ★★ same condition
ACAT1 c.120+1G>C Likely pathogenic ★★ same condition
ACAT1 c.121-3C>G Pathogenic/Likely pathogenic ★★ same condition
ACAT1 c.238+2T>A Pathogenic/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-ala348 (accessed [today's date]).

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