Is ACAT1 p.Val187= (c.561C>G) pathogenic?

ACAT1 p.Val187= (c.561C>G) is classified Uncertain significance in ACAT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-03). Very rare (popmax 0.00134%, afr); Associated with beta-ketothiolase deficiency.

What condition is associated with ACAT1 p.Val187= (c.561C>G)?

ACAT1 p.Val187= (c.561C>G) is associated with beta-ketothiolase deficiency (ClinVar).

How common is ACAT1 p.Val187= (c.561C>G) in the general population?

ACAT1 p.Val187= (c.561C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Beta-ketothiolase deficiency inherited?

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

ACAT1 p.Val187=

c.561C>G · VCV4065523

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

beta-ketothiolase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.056	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 2.6, phastCons 1
Overall
CADD	13.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,888 alleles

Overall 0.000186% 3/1,613,948 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-Americangrpmax	0.00134%	74,888
European (non-Finnish)	8.47e-05%	1,180,013

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val187=
Coding: c.561C>G
MANE Select: NM_003101 · reported on NM_000019
Type: single nucleotide variant
Location: chr11:108139023 (GRCh38)
Structure: AlphaFold pLDDT 81.22 · 5 PDB
Residue 187: 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 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-val187 (accessed [today's date]).

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