Is ACAA2 p.Leu32Val (c.94T>G) pathogenic?

ACAA2 p.Leu32Val (c.94T>G) is classified Uncertain significance in ACAA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-18). AlphaMissense: ambiguous (0.3577); Absent from gnomAD v4.1.

How common is ACAA2 p.Leu32Val (c.94T>G) in the general population?

ACAA2 p.Leu32Val (c.94T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAA2 p.Leu32Val (c.94T>G)?

AlphaMissense predicts ambiguous (score 0.3577) — an in-silico prediction, not a clinical call.

ACAA2 p.Leu32Val

c.94T>G · rs2511373502 · VCV3133444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3577 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3577	ambiguous
REVEL	0.708	pathogenic-leaning
SaProt	LLR -11.49	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP -5.9
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.51 · regional, not allelic
Overall
CADD	19.57	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

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: ACAA2
Protein: p.Leu32Val
Coding: c.94T>G
MANE Select: NM_006111
dbSNP: rs2511373502
Type: single nucleotide variant
Location: chr18:49802776 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.49 · 2 PDB
Residue 32: an α-helix

Full ACAA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAA2 p.Tyr198Asn Benign ★★ same type
ACAA2 p.Ala183Thr Uncertain significance ★ ⚠ same type
ACAA2 p.Ala196Thr Uncertain significance ★ ⚠ same type
ACAA2 p.Ala250Thr Uncertain significance ★ ⚠ same type
ACAA2 p.Ala267Gly Uncertain significance ★ ⚠ same type
ACAA2 p.Ala70Ser Uncertain significance ★ ⚠ same type
ACAA2 p.Arg133His Uncertain significance ★ ⚠ same type
ACAA2 p.Arg371Cys 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/acaa2-p-leu32val (accessed [today's date]).

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