Is ACAT2 p.Val99Met (c.295G>A) pathogenic?

ACAT2 p.Val99Met (c.295G>A) is classified Uncertain significance in ACAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.3041); Absent from gnomAD v4.1.

How common is ACAT2 p.Val99Met (c.295G>A) in the general population?

ACAT2 p.Val99Met (c.295G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAT2 p.Val99Met (c.295G>A)?

AlphaMissense predicts likely benign (score 0.3041) — an in-silico prediction, not a clinical call.

ACAT2 p.Val99Met

c.295G>A · VCV3997422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3041 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3041	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	28.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACAT2
Protein: p.Val99Met
Coding: c.295G>A
MANE Select: NM_003578 · reported on NM_005891
Type: single nucleotide variant
Location: chr6:159767109 (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-val99met (accessed [today's date]).

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