Is CPT2 p.Leu358Arg (c.1073T>G) pathogenic?

CPT2 p.Leu358Arg (c.1073T>G) is classified Uncertain significance in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely pathogenic (0.9545); Absent from gnomAD v4.1.

How common is CPT2 p.Leu358Arg (c.1073T>G) in the general population?

CPT2 p.Leu358Arg (c.1073T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPT2 p.Leu358Arg (c.1073T>G)?

AlphaMissense predicts likely pathogenic (score 0.9545) — an in-silico prediction, not a clinical call.

CPT2 p.Leu358Arg

c.1073T>G · VCV3902115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9545 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9545	likely pathogenic · top 9% in CPT2
REVEL	0.96	strongly pathogenic-leaning
SaProt	LLR -16.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CPT2
Protein: p.Leu358Arg
Coding: c.1073T>G
MANE Select: NM_000098
Type: single nucleotide variant
Location: chr1:53210747 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPT2 p.Leu358= Likely benign ★ same residue
CPT2 p.Leu358Phe Uncertain significance ⚠ same residue
CPT2 c.340+1G>C Pathogenic/Likely pathogenic ★★ same type
CPT2 c.340+5G>A Likely pathogenic ★★ same type
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same type
CPT2 p.Ala67Gly Likely pathogenic ★★ ⚠ same type
CPT2 p.Arg124Gln Likely pathogenic ★★ ⚠ same type
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ 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/cpt2-p-leu358arg (accessed [today's date]).

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