Is ACAT1 p.Met1Val (c.1A>G) pathogenic?

ACAT1 p.Met1Val (c.1A>G) is classified Pathogenic in ACAT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-05). Very rare (popmax 0.00238%, sas); Associated with beta-ketothiolase deficiency.

What condition is associated with ACAT1 p.Met1Val (c.1A>G)?

ACAT1 p.Met1Val (c.1A>G) is associated with beta-ketothiolase deficiency (ClinVar).

How common is ACAT1 p.Met1Val (c.1A>G) in the general population?

ACAT1 p.Met1Val (c.1A>G) is very rare (popmax 0.00238%, sas) (gnomAD).

How is Beta-ketothiolase deficiency inherited?

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

ACAT1 p.Met1Val

c.1A>G · rs1305448140 · VCV666460

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00238%, sas)

Conditions

beta-ketothiolase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.559	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2, phastCons 1
Overall
CADD	19.19	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% South Asian · 2/84,086 alleles

Filtering AF 0.000515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.00093% 13/1,398,408 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00238%	42,043
European (non-Finnish)	0.000959%	104,296

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.Met1Val
Coding: c.1A>G
MANE Select: NM_003101 · reported on NM_000019
dbSNP: rs1305448140
Type: single nucleotide variant
Location: chr11:108121607 (GRCh38)
Structure: AlphaFold pLDDT 81.22 · 5 PDB
Residue 1: the 'disordered' region; a modified residue (n-acetylmethionine)

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.Met1Leu Pathogenic/Likely pathogenic ★★ same residue
ACAT1 p.Met1Thr Pathogenic ★★ same residue
ACAT1 p.Met1Lys 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

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-met1val (accessed [today's date]).

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