Is ACAT1 p.Ser157= (c.471C>A) pathogenic?

ACAT1 p.Ser157= (c.471C>A) is classified Benign in ACAT1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 19.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with beta-ketothiolase deficiency.

What condition is associated with ACAT1 p.Ser157= (c.471C>A)?

ACAT1 p.Ser157= (c.471C>A) 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.Ser157=

Q: How common is ACAT1 p.Ser157= (c.471C>A) in the general population?

ACAT1 p.Ser157= (c.471C>A) is common (popmax 19.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.471C>A · rs35188041 · VCV92296

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 19.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

beta-ketothiolase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.049	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.1, phastCons 1
Overall
CADD	9.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.7% African / African-American · 14,735/74,924 alleles

Filtering AF 19.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.3%

Overall 17% 274,746/1,613,768 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.7%	5
Amishnot grpmax-eligible	18.2%	6
European (non-Finnish)	17.8%	6
South Asian	16.6%	6
Finnishnot grpmax-eligible	16.2%	6
Remaining individualsnot grpmax-eligible	16%	6
Ashkenazi Jewishnot grpmax-eligible	15.5%	6
Admixed American	11.4%	9
Middle Eastern	10.4%	10
East Asian	3.83%	26

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.Ser157=
Coding: c.471C>A
MANE Select: NM_003101 · reported on NM_000019
dbSNP: rs35188041
Type: single nucleotide variant
Location: chr11:108138933 (GRCh38)
Structure: AlphaFold pLDDT 81.22 · 5 PDB
Residue 157: 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-ser157 (accessed [today's date]).

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