Is ACAA1 p.Pro363Arg (c.1088C>G) pathogenic?

ACAA1 p.Pro363Arg (c.1088C>G) is classified Uncertain significance in ACAA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely benign (0.0908); Absent from gnomAD v4.1.

How common is ACAA1 p.Pro363Arg (c.1088C>G) in the general population?

ACAA1 p.Pro363Arg (c.1088C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAA1 p.Pro363Arg (c.1088C>G)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

ACAA1 p.Pro363Arg

c.1088C>G · VCV3454717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,446)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -9.62	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 0.14	GERP -3.6
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.034 · regional, not allelic
Overall
CADD	8.615	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

No allele count reported in gnomAD v4.1 (AN 1,599,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACAA1
Protein: p.Pro363Arg
Coding: c.1088C>G
MANE Select: NM_001607
Type: single nucleotide variant
Location: chr3:38125676 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 2 PDB
Residue 363: an α-helix

Full ACAA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAA1 p.Pro363Ala Uncertain significance ★ ⚠ same residue
ACAA1 p.Glu172Asp Benign ★★ ⚠ same type
ACAA1 p.Ala131Ser Uncertain significance ★ ⚠ same type
ACAA1 p.Ala24Val Uncertain significance ★ ⚠ same type
ACAA1 p.Ala324Gly Uncertain significance ★ ⚠ same type
ACAA1 p.Ala33Thr Uncertain significance ★ ⚠ same type
ACAA1 p.Ala416Thr Uncertain significance ★ ⚠ same type
ACAA1 p.Arg167Cys 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/acaa1-p-pro363arg (accessed [today's date]).

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