Is ACAT2 p.Pro204Gln (c.611C>A) pathogenic?

ACAT2 p.Pro204Gln (c.611C>A) is classified Uncertain significance in ACAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.3288); Very rare (popmax 0.000169%, nfe).

How common is ACAT2 p.Pro204Gln (c.611C>A) in the general population?

ACAT2 p.Pro204Gln (c.611C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ACAT2 p.Pro204Gln (c.611C>A)?

AlphaMissense predicts likely benign (score 0.3288) — an in-silico prediction, not a clinical call.

ACAT2 p.Pro204Gln

c.611C>A · VCV4636671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3288	likely benign
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -13.30	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.6, phastCons 0.99
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,006 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,828 alleles · very rare

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.Pro204Gln
Coding: c.611C>A
MANE Select: NM_003578 · reported on NM_005891
Type: single nucleotide variant
Location: chr6:159775290 (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-pro204gln (accessed [today's date]).

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