Is CPT1A p.Arg339Ter (c.1015C>T) pathogenic?

CPT1A p.Arg339Ter (c.1015C>T) is classified Pathogenic in CPT1A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-03-27). Very rare (popmax 0.00223%, eas); Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Arg339Ter (c.1015C>T)?

CPT1A p.Arg339Ter (c.1015C>T) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Arg339Ter (c.1015C>T) in the general population?

CPT1A p.Arg339Ter (c.1015C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Carnitine palmitoyl transferase 1A deficiency inherited?

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

CPT1A p.Arg339Ter

c.1015C>T · rs1435045544 · VCV1070426

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

carnitine palmitoyl transferase 1A deficiency

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 10 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -3.8
Overall
CADD	34.0	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 0.00223% East Asian · 1/44,876 alleles

Overall 0.000205% 3/1,461,746 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
South Asian	0.0011%	91,076
European (non-Finnish)	8.47e-05%	1,180,026

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: CPT1A
Protein: p.Arg339Ter
Coding: c.1015C>T
MANE Select: NM_001876
dbSNP: rs1435045544
Type: single nucleotide variant
Location: chr11:68784963 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.55 · 1 PDB

Full CPT1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

carnitine palmitoyl transferase 1A deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Carnitine palmitoyl transferase 1A deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CPT1A c.1163+1G>A Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.1163+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.1352+1G>C Likely pathogenic ★★ same condition
CPT1A c.1459-1G>A Likely pathogenic ★★ same condition
CPT1A c.1575+1G>T Likely pathogenic ★★ same condition
CPT1A c.2028+2T>G Likely pathogenic ★★ same condition
CPT1A c.281+1G>A Pathogenic ★★ same condition
CPT1A c.693+1G>A 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/cpt1a-p-arg339ter (accessed [today's date]).

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