Is CPT2 p.Ser408fs (c.1223_1224del) pathogenic?

CPT2 p.Ser408fs (c.12231224del) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-16). Very rare (popmax 8.47e-05%, nfe); Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Ser408fs (c.1223_1224del)?

CPT2 p.Ser408fs (c.1223_1224del) is associated with carnitine palmitoyltransferase II deficiency (ClinVar).

How common is CPT2 p.Ser408fs (c.1223_1224del) in the general population?

CPT2 p.Ser408fs (c.1223_1224del) is very rare (popmax 8.47e-05%, 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.Ser408fs

c.1223_1224del · rs752373512 · VCV1172859

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,994 alleles

Overall 6.2e-05% 1/1,614,004 alleles · very rare exomes 1/1,461,890 · genomes 0/152,114 · joint denominator

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.Ser408fs
Coding: c.1223_1224del
MANE Select: NM_000098
dbSNP: rs752373512
Type: Microsatellite
Location: chr1:53210895 (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

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Cys326fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.His523fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Leu199fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Leu72fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ser38fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Gly451fs Pathogenic ★ same condition
CPT2 p.Glu545del Uncertain significance ★ same condition
CPT2 p.Leu244del Uncertain significance ★ 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-ser408fs (accessed [today's date]).

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