Is CPT2 p.Glu81fs (c.241_242del) pathogenic?

CPT2 p.Glu81fs (c.241242del) is classified Likely pathogenic in CPT2 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.0011%, sas); Associated with carnitine palmitoyl transferase II deficiency, severe infantile form.

What condition is associated with CPT2 p.Glu81fs (c.241_242del)?

CPT2 p.Glu81fs (c.241_242del) is associated with carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

How common is CPT2 p.Glu81fs (c.241_242del) in the general population?

CPT2 p.Glu81fs (c.241_242del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Glu81fs

c.241_242del · rs1645358577 · VCV917934

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

carnitine palmitoyl transferase II deficiency, severe infantile form

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 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,044 alleles

Overall 6.85e-05% 1/1,460,720 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.Glu81fs
Coding: c.241_242del
MANE Select: NM_000098
dbSNP: rs1645358577
Type: Deletion
Location: chr1:53202329 (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

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.Gln33fs Pathogenic ★★ same condition
CPT2 p.Glu285fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Leu556fs Pathogenic ★★ same condition
CPT2 p.Leu592fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Lys414fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Phe516fs Pathogenic ★★ same condition
CPT2 p.Phe602fs 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-glu81fs (accessed [today's date]).

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