Is CPT2 p.Lys414fs (c.1239_1240del) pathogenic?

CPT2 p.Lys414fs (c.12391240del) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-02). Very rare (popmax 0.00178%, nfe); Associated with Acute rhabdomyolysis.

How common is CPT2 p.Lys414fs (c.1239_1240del) in the general population?

CPT2 p.Lys414fs (c.1239_1240del) is very rare (popmax 0.00178%, nfe) (gnomAD).

CPT2 p.Lys414fs

Q: What condition is associated with CPT2 p.Lys414fs (c.1239_1240del)?

CPT2 p.Lys414fs (c.1239_1240del) is associated with Acute rhabdomyolysis, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.1239_1240del · rs397509431 · VCV92430

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

Acute rhabdomyolysis

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 1.4	GERP 2.4, phastCons 1
Overall
CADD	24.9	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 0.00178% European (non-Finnish) · 21/1,180,048 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00097%

Overall 0.0119% 192/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.507%	197
Remaining individualsnot grpmax-eligible	0.0336%	2,976
European (non-Finnish)grpmax	0.00178%	56,193

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys414fs
Coding: c.1239_1240del
MANE Select: NM_000098
dbSNP: rs397509431
Type: Deletion
Location: chr1:53210912 (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

Acute rhabdomyolysis — 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 carnitine palmitoyltransferase II deficiency

Similar variants

CPT2 p.Lys414= Conflicting classifications of pathogenicity ★ same residue
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

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-lys414fs (accessed [today's date]).

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