Is CPT2 p.Arg151Gln (c.452G>A) pathogenic?

CPT2 p.Arg151Gln (c.452G>A) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-22). AlphaMissense: ambiguous (0.455); Very rare (popmax 0.00223%, eas); Associated with carnitine palmitoyl transferase II deficiency, myopathic form.

What condition is associated with CPT2 p.Arg151Gln (c.452G>A)?

CPT2 p.Arg151Gln (c.452G>A) is associated with carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form, carnitine palmitoyl transferase II deficiency, neonatal form (ClinVar).

How common is CPT2 p.Arg151Gln (c.452G>A) in the general population?

CPT2 p.Arg151Gln (c.452G>A) is very rare (popmax 0.00223%, eas) (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.Arg151Gln (c.452G>A)?

AlphaMissense predicts ambiguous (score 0.455) — an in-silico prediction, not a clinical call.

CPT2 p.Arg151Gln

c.452G>A · rs515726177 · VCV130889

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

ambiguous

0.455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

carnitine palmitoyl transferase II deficiency, myopathic form

Computational evidence

Protein change
AlphaMissense	0.455	ambiguous
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	29.2	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 · 1/44,876 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00136% 22/1,613,842 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.00153%	65,556
South Asian	0.0011%	91,084

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.Arg151Gln
Coding: c.452G>A
MANE Select: NM_000098
dbSNP: rs515726177
Type: single nucleotide variant
Location: chr1:53210126 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 151: a UniProt-annotated variant site (in cpt2d)

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

carnitine palmitoyl transferase II deficiency, myopathic form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 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

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Arg151Trp Pathogenic ★★ same residue
CPT2 p.Arg151= 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-arg151gln (accessed [today's date]).

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