Is CPT2 p.Gln459Ter (c.1375C>T) pathogenic?

CPT2 p.Gln459Ter (c.1375C>T) is classified Likely pathogenic in CPT2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-11-02). Absent from gnomAD v4.1; Associated with carnitine palmitoyl transferase II deficiency, severe infantile form.

What condition is associated with CPT2 p.Gln459Ter (c.1375C>T)?

CPT2 p.Gln459Ter (c.1375C>T) is associated with carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

How common is CPT2 p.Gln459Ter (c.1375C>T) in the general population?

CPT2 p.Gln459Ter (c.1375C>T) is absent from gnomAD v4.1 (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Gln459Ter

c.1375C>T · rs1553169771 · VCV554750

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.29, phastCons 1
Overall
CADD	37.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPT2
Protein: p.Gln459Ter
Coding: c.1375C>T
MANE Select: NM_000098
dbSNP: rs1553169771
Type: single nucleotide variant
Location: chr1:53211049 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 459: a binding site

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.Gln459Leu Uncertain significance ★★ ⚠ same residue
CPT2 c.340+5G>A Likely pathogenic ★★ same condition
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ala67Gly Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Gln Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg151Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg151Trp 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-gln459ter (accessed [today's date]).

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