Is CPT1A p.Pro681fs (c.2042_2049del) pathogenic?

CPT1A p.Pro681fs (c.20422049del) is classified Likely pathogenic in CPT1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Pro681fs (c.2042_2049del)?

CPT1A p.Pro681fs (c.2042_2049del) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How is Carnitine palmitoyl transferase 1A deficiency inherited?

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

CPT1A p.Pro681fs

c.2042_2049del · VCV4814973

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

carnitine palmitoyl transferase 1A 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	predicted	premature termination codon in exon 17 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.7	GERP -4.1

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

Variant & gene context

Gene: CPT1A
Protein: p.Pro681fs
Coding: c.2042_2049del
MANE Select: NM_001876
Type: Deletion
Location: chr11:68760318 (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 p.Pro672_Phe673insTer Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.556-12del Benign ★★ same condition
CPT1A c.1576-9_1587del Likely pathogenic ★ same condition
CPT1A p.Asn404fs Pathogenic ★ same condition
CPT1A p.Gln188fs Pathogenic ★ same condition
CPT1A p.Gln628fs Likely pathogenic ★ same condition
CPT1A p.Glu196fs Pathogenic ★ same condition
CPT1A p.Glu372fs 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-pro681fs (accessed [today's date]).

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