Is ACAT1 p.Leu7= (c.21T>G) pathogenic?

ACAT1 p.Leu7= (c.21T>G) is classified Likely benign in ACAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). Absent from gnomAD v4.1; Associated with beta-ketothiolase deficiency.

What condition is associated with ACAT1 p.Leu7= (c.21T>G)?

ACAT1 p.Leu7= (c.21T>G) is associated with beta-ketothiolase deficiency (ClinVar).

How common is ACAT1 p.Leu7= (c.21T>G) in the general population?

ACAT1 p.Leu7= (c.21T>G) is absent from gnomAD v4.1 (gnomAD).

How is Beta-ketothiolase deficiency inherited?

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

ACAT1 p.Leu7=

c.21T>G · rs2496515785 · VCV2019720

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -1.1	GERP -4
Overall
CADD	14.44	PHRED · no single calibrated threshold — expert panels disagree

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: ACAT1
Protein: p.Leu7=
Coding: c.21T>G
MANE Select: NM_003101 · reported on NM_000019
dbSNP: rs2496515785
Type: single nucleotide variant
Location: chr11:108121627 (GRCh38)
Structure: AlphaFold pLDDT 81.22 · 5 PDB
Residue 7: the 'disordered' region

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 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
ACAT1 c.435+1G>A 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-leu7 (accessed [today's date]).

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