Is CPT2 p.Trp116Ter (c.347G>A) pathogenic?

CPT2 p.Trp116Ter (c.347G>A) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-07-24). Very rare (popmax 0.000254%, nfe); Associated with carnitine palmitoyl transferase II deficiency, neonatal form.

How common is CPT2 p.Trp116Ter (c.347G>A) in the general population?

CPT2 p.Trp116Ter (c.347G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Trp116Ter

Q: What condition is associated with CPT2 p.Trp116Ter (c.347G>A)?

CPT2 p.Trp116Ter (c.347G>A) is associated with carnitine palmitoyl transferase II deficiency, neonatal form, carnitine palmitoyltransferase II deficiency (ClinVar).

c.347G>A · rs1645411052 · VCV1357197

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

carnitine palmitoyl transferase II deficiency, neonatal 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 12	GERP 2.4, phastCons 1
Overall
CADD	38.0	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

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,454 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,246 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)grpmax	0.000254%	393,151

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.Trp116Ter
Coding: c.347G>A
MANE Select: NM_000098
dbSNP: rs1645411052
Type: single nucleotide variant
Location: chr1:53210021 (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, neonatal form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyltransferase II deficiency

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 c.340+1G>C Pathogenic/Likely pathogenic ★★ same condition
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-trp116ter (accessed [today's date]).

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