Is CPT2 p.Val507Leu (c.1519G>C) pathogenic?

CPT2 p.Val507Leu (c.1519G>C) is classified Uncertain significance in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: likely benign (0.0888); Absent from gnomAD v4.1; Associated with carnitine palmitoyl transferase II deficiency, severe infantile form.

What condition is associated with CPT2 p.Val507Leu (c.1519G>C)?

CPT2 p.Val507Leu (c.1519G>C) is associated with carnitine palmitoyl transferase II deficiency, severe infantile form, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, neonatal form (ClinVar).

How common is CPT2 p.Val507Leu (c.1519G>C) in the general population?

CPT2 p.Val507Leu (c.1519G>C) is absent from gnomAD v4.1 (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CPT2 p.Val507Leu (c.1519G>C)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

CPT2 p.Val507Leu

c.1519G>C · VCV3585909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase II deficiency, severe infantile form

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -6.68	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 -10	GERP -4.3
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	0.297	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: CPT2
Protein: p.Val507Leu
Coding: c.1519G>C
MANE Select: NM_000098
Type: single nucleotide variant
Location: chr1:53211193 (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

Disease context

carnitine palmitoyl transferase II deficiency, severe infantile form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyl transferase II deficiency, myopathic form carnitine palmitoyl transferase II deficiency, neonatal form encephalopathy, acute, infection-induced, susceptibility to, 4

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Val507Gly Uncertain significance ★ ⚠ same residue
CPT2 p.Val507Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
CPT2 p.Val507= Likely benign ★ same residue
CPT2 c.340+5G>A Likely pathogenic ★★ same condition
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ala67Gly Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Gln Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ same condition

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-val507leu (accessed [today's date]).

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