Is CPT2 p.Ser38fs (c.110_111dup) pathogenic?

CPT2 p.Ser38fs (c.110111dup) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-13). Ultra-rare (popmax 0.0157%, amr); Associated with CPT2-related disorder.

How common is CPT2 p.Ser38fs (c.110_111dup) in the general population?

CPT2 p.Ser38fs (c.110_111dup) is ultra-rare (popmax 0.0157%, amr) (gnomAD).

CPT2 p.Ser38fs

Q: What condition is associated with CPT2 p.Ser38fs (c.110_111dup)?

CPT2 p.Ser38fs (c.110_111dup) is associated with CPT2-related disorder, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.110_111dup · rs754363068 · VCV371697

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, amr)

Conditions

CPT2-related disorder

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 9.1	GERP 1, phastCons 1
Overall
CADD	33.0	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 0.0157% Admixed American · 8/50,984 alleles

Filtering AF 0.00772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00149% 23/1,538,902 alleles · ultra-rare exomes 21/1,386,844 · genomes 2/152,058 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0157%	6,373
Remaining individualsnot grpmax-eligible	0.00334%	29,982
African / African-American	0.00137%	72,940
European (non-Finnish)	0.00105%	95,531

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.Ser38fs
Coding: c.110_111dup
MANE Select: NM_000098
dbSNP: rs754363068
Type: Microsatellite
Location: chr1:53197050 (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

CPT2-related disorder

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

Similar variants

CPT2 p.Cys326fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.His523fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Leu199fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Leu72fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ser408fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg511fs Likely pathogenic ★ same condition
CPT2 p.Gln400fs Likely pathogenic ★ same condition
CPT2 p.Gly249fs 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-ser38fs (accessed [today's date]).

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