Is ACAT2 p.Val261= (c.783C>T) pathogenic?

ACAT2 p.Val261= (c.783C>T) is classified Benign in ACAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Common (popmax 38.4%, eas) — too common for a highly-penetrant pathogenic allele.

ACAT2 p.Val261=

Q: How common is ACAT2 p.Val261= (c.783C>T) in the general population?

ACAT2 p.Val261= (c.783C>T) is common (popmax 38.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.783C>T · VCV4683232

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 38.4%, eas) — too common for a highly-penetrant pathogenic allele

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 6.7	GERP -2.3, phastCons 1
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38.4% East Asian · 17,246/44,868 alleles

Filtering AF 38% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.8%

Overall 20% 322,132/1,613,396 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	38.4%	3
South Asian	26.8%	4
Finnishnot grpmax-eligible	24.5%	4
Middle Eastern	20.9%	5
Remaining individualsnot grpmax-eligible	20%	5
European (non-Finnish)	18.9%	5
Admixed American	18.6%	5
African / African-American	18.1%	6
Amishnot grpmax-eligible	12.4%	8
Ashkenazi Jewishnot grpmax-eligible	12.4%	8

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: ACAT2
Protein: p.Val261=
Coding: c.783C>T
MANE Select: NM_003578 · reported on NM_005891
Type: single nucleotide variant
Location: chr6:159777327 (GRCh38)
Structure: AlphaFold pLDDT 82.59 · 2 PDB

Full ACAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SOAT2 p.Ala67= Benign ★★ same type
SOAT2 p.Leu402= Benign ★★ same type
ACAT2 p.Ala230Pro Uncertain significance ★ ⚠ same type
ACAT2 p.Ala323Gly Uncertain significance ★ ⚠ same type
ACAT2 p.Ala330Val Uncertain significance ★ ⚠ same type
ACAT2 p.Ala348Ser Uncertain significance ★ ⚠ same type
ACAT2 p.Ala357Gly Uncertain significance ★ ⚠ same type
ACAT2 p.Arg223His Uncertain significance ★ ⚠ same type

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/acat2-p-val261 (accessed [today's date]).

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