Is CPT2 p.Val606fs (c.1816_1817del) pathogenic?

CPT2 p.Val606fs (c.18161817del) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-03). Very rare (popmax 0.000424%, nfe); Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Val606fs (c.1816_1817del)?

CPT2 p.Val606fs (c.1816_1817del) is associated with carnitine palmitoyltransferase II deficiency, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

How common is CPT2 p.Val606fs (c.1816_1817del) in the general population?

CPT2 p.Val606fs (c.1816_1817del) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Val606fs

c.1816_1817del · rs908749525 · VCV845527

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.72	GERP -1.8, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,056 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,134 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CPT2
Protein: p.Val606fs
Coding: c.1816_1817del
MANE Select: NM_000098
dbSNP: rs908749525
Type: Deletion
Location: chr1:53213434 (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 palmitoyltransferase II deficiency — 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, severe infantile 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.Ala643_Leu644insTer Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg382fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Asp576fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Gln33fs Pathogenic ★★ same condition
CPT2 p.Glu285fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Leu178_Pro180delinsPhe Pathogenic ★★ same condition
CPT2 p.Leu556fs Pathogenic ★★ same condition
CPT2 p.Leu575fs 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-val606fs (accessed [today's date]).

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