Is CPT2 p.Arg151Trp (c.451C>T) pathogenic?

CPT2 p.Arg151Trp (c.451C>T) is classified Pathogenic in CPT2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-05). AlphaMissense: likely pathogenic (0.6937); Very rare (popmax 0.005%, amr); Associated with CPT2-related disorder.

How common is CPT2 p.Arg151Trp (c.451C>T) in the general population?

CPT2 p.Arg151Trp (c.451C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CPT2 p.Arg151Trp (c.451C>T)?

AlphaMissense predicts likely pathogenic (score 0.6937) — an in-silico prediction, not a clinical call.

CPT2 p.Arg151Trp

Q: What condition is associated with CPT2 p.Arg151Trp (c.451C>T)?

CPT2 p.Arg151Trp (c.451C>T) is associated with CPT2-related disorder, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.451C>T · rs200080591 · VCV1358726

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.6937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPT2-related disorder

Computational evidence

Protein change
AlphaMissense	0.6937	likely pathogenic ✓ concordant with ClinVar
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -13.86	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 1.3	GERP -3.6, phastCons 0.59
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	22.7	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 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00186% 30/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0219%	4,573
Admixed Americangrpmax	0.005%	20,000
European (non-Finnish)	0.0011%	90,772

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg151Trp
Coding: c.451C>T
MANE Select: NM_000098
dbSNP: rs200080591
Type: single nucleotide variant
Location: chr1:53210125 (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

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.Arg151Gln Pathogenic/Likely 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-arg151trp (accessed [today's date]).

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