Is CPT2 p.Arg503Cys (c.1507C>T) pathogenic?

CPT2 p.Arg503Cys (c.1507C>T) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-27). AlphaMissense: likely pathogenic (0.8564); Very rare (popmax 0.00223%, eas); Associated with CPT2-related disorder.

How common is CPT2 p.Arg503Cys (c.1507C>T) in the general population?

CPT2 p.Arg503Cys (c.1507C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CPT2 p.Arg503Cys (c.1507C>T)?

AlphaMissense predicts likely pathogenic (score 0.8564) — an in-silico prediction, not a clinical call.

CPT2 p.Arg503Cys

Q: What condition is associated with CPT2 p.Arg503Cys (c.1507C>T)?

CPT2 p.Arg503Cys (c.1507C>T) is associated with CPT2-related disorder, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.1507C>T · rs74315296 · VCV8959

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.8564 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPT2-related disorder

Computational evidence

Protein change
AlphaMissense	0.8564	likely pathogenic ✓ concordant with ClinVar
REVEL	0.968	strongly pathogenic-leaning
SaProt	LLR -12.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	28.8	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

Grpmax group 0.00223% East Asian · 1/44,786 alleles

Filtering AF 0.000805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000652%

Overall 0.00131% 21/1,608,362 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,786
Admixed American	0.00167%	59,808
Remaining individualsnot grpmax-eligible	0.00161%	62,204
European (non-Finnish)	0.00136%	73,508
African / African-American	0.00134%	74,816
South Asian	0.0011%	90,554

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.Arg503Cys
Coding: c.1507C>T
MANE Select: NM_000098
dbSNP: rs74315296
Type: single nucleotide variant
Location: chr1:53211181 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 503: a UniProt-annotated variant site (in cpt2d)

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.Arg503His Uncertain significance ★★ ⚠ same residue
CPT2 p.Arg503= 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
CPT2 p.Arg124Ter 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/cpt2-p-arg503cys (accessed [today's date]).

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