Is CPT2 p.Phe557fs (c.1669_1672del) pathogenic?

CPT2 p.Phe557fs (c.16691672del) is classified Likely pathogenic in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Phe557fs (c.1669_1672del)?

CPT2 p.Phe557fs (c.1669_1672del) is associated with carnitine palmitoyltransferase II deficiency (ClinVar).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Phe557fs

c.1669_1672del · VCV4817417

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 0.003	GERP -4.2, phastCons 0.068

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

Variant & gene context

Gene: CPT2
Protein: p.Phe557fs
Coding: c.1669_1672del
MANE Select: NM_000098
Type: Deletion
Location: chr1:53213284 (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.Phe557Tyr Uncertain significance ★ ⚠ same residue
CPT2 p.Phe557= Likely benign ★ 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.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-phe557fs (accessed [today's date]).

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