Is CPT2 p.Ser48Arg (c.144C>A) pathogenic?

CPT2 p.Ser48Arg (c.144C>A) is classified Uncertain significance in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.9839); No allele count reported in gnomAD v4.1 (AN 1,538,800); Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Ser48Arg (c.144C>A)?

CPT2 p.Ser48Arg (c.144C>A) is associated with carnitine palmitoyltransferase II deficiency (ClinVar).

How common is CPT2 p.Ser48Arg (c.144C>A) in the general population?

CPT2 p.Ser48Arg (c.144C>A) is no allele count reported in gnomAD v4.1 (AN 1,538,800) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

What do computational predictors say about CPT2 p.Ser48Arg (c.144C>A)?

AlphaMissense predicts likely pathogenic (score 0.9839) — an in-silico prediction, not a clinical call.

CPT2 p.Ser48Arg

c.144C>A · rs2100255084 · VCV1428330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9839 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,538,800)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
AlphaMissense	0.9839	likely pathogenic · top 4% in CPT2
REVEL	0.728	pathogenic-leaning
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.53	GERP -3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,538,800). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CPT2
Protein: p.Ser48Arg
Coding: c.144C>A
MANE Select: NM_000098
dbSNP: rs2100255084
Type: single nucleotide variant
Location: chr1:53197087 (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 palmitoyltransferase II deficiency — 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.Ser48Asn Uncertain significance ★ ⚠ same residue
CPT2 p.Ser48Thr Uncertain significance ★ ⚠ same residue
CPT2 p.Ser48= Likely benign ★ same residue
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

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-ser48arg (accessed [today's date]).

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