Is CPT2 p.Gln33fs (c.98del) pathogenic?

CPT2 p.Gln33fs (c.98del) is classified Pathogenic in CPT2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0157%, amr); Associated with carnitine palmitoyl transferase II deficiency, severe infantile form.

What condition is associated with CPT2 p.Gln33fs (c.98del)?

CPT2 p.Gln33fs (c.98del) is associated with carnitine palmitoyl transferase II deficiency, severe infantile form, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, neonatal form (ClinVar).

How common is CPT2 p.Gln33fs (c.98del) in the general population?

CPT2 p.Gln33fs (c.98del) is ultra-rare (popmax 0.0157%, amr) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Gln33fs

c.98del · rs917744011 · VCV495549

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, amr)

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 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP 0.14, phastCons 0.99
Overall
CADD	27.8	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 0.0157% Admixed American · 8/50,960 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00104% 16/1,538,348 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0157%	6,370
Remaining individualsnot grpmax-eligible	0.00834%	11,987
European (non-Finnish)	0.000262%	382,066

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.Gln33fs
Coding: c.98del
MANE Select: NM_000098
dbSNP: rs917744011
Type: Deletion
Location: chr1:53197041 (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

Also linked: carnitine palmitoyl transferase II deficiency, myopathic form carnitine palmitoyl transferase II deficiency, neonatal form encephalopathy, acute, infection-induced, susceptibility to, 4 carnitine palmitoyltransferase II deficiency

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Gln33His Uncertain significance ★★ ⚠ 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.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-gln33fs (accessed [today's date]).

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