Is ACAT2 p.Asn22Ser (c.65A>G) pathogenic?

ACAT2 p.Asn22Ser (c.65A>G) is classified Uncertain significance in ACAT2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-20). AlphaMissense: likely benign (0.0832); Ultra-rare (popmax 0.0923%, amr).

How common is ACAT2 p.Asn22Ser (c.65A>G) in the general population?

ACAT2 p.Asn22Ser (c.65A>G) is ultra-rare (popmax 0.0923%, amr) (gnomAD).

What do computational predictors say about ACAT2 p.Asn22Ser (c.65A>G)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

ACAT2 p.Asn22Ser

c.65A>G · rs199953042 · VCV3135833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0923%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -8.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.56, phastCons 1
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0923% Admixed American · 55/59,620 alleles

Filtering AF 0.0727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0658%

Overall 0.01% 162/1,612,304 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0923%	1,084
Finnishnot grpmax-eligible	0.0219%	4,569
Remaining individualsnot grpmax-eligible	0.0128%	7,798
South Asian	0.0088%	11,367
East Asian	0.00668%	14,961
European (non-Finnish)	0.00611%	16,378
African / African-American	0.00267%	37,453

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.Asn22Ser
Coding: c.65A>G
MANE Select: NM_003578 · reported on NM_005891
dbSNP: rs199953042
Type: single nucleotide variant
Location: chr6:159762928 (GRCh38)
Structure: AlphaFold pLDDT 82.59 · 2 PDB
Residue 22: the 'disordered' region

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

Similar variants

ACAT2 p.Asn22Thr Uncertain significance ★ ⚠ same residue
SOAT2 p.Arg22His Likely benign ★ ⚠ same residue
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

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-asn22ser (accessed [today's date]).

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