Is CPT2 p.Pro571Arg (c.1712C>G) pathogenic?

CPT2 p.Pro571Arg (c.1712C>G) is classified Uncertain significance in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: likely pathogenic (0.6827); Absent from gnomAD v4.1; Associated with carnitine palmitoyl transferase II deficiency, neonatal form.

What condition is associated with CPT2 p.Pro571Arg (c.1712C>G)?

CPT2 p.Pro571Arg (c.1712C>G) is associated with carnitine palmitoyl transferase II deficiency, neonatal form (ClinVar).

How common is CPT2 p.Pro571Arg (c.1712C>G) in the general population?

CPT2 p.Pro571Arg (c.1712C>G) is absent from gnomAD v4.1 (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.Pro571Arg (c.1712C>G)?

AlphaMissense predicts likely pathogenic (score 0.6827) — an in-silico prediction, not a clinical call.

CPT2 p.Pro571Arg

c.1712C>G · rs2525596135 · VCV1705374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6827 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase II deficiency, neonatal form

Computational evidence

Protein change
AlphaMissense	0.6827	likely pathogenic
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -14.36	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPT2
Protein: p.Pro571Arg
Coding: c.1712C>G
MANE Select: NM_000098
dbSNP: rs2525596135
Type: single nucleotide variant
Location: chr1:53213330 (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 palmitoyl transferase II deficiency, neonatal form — 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.Pro571Thr Pathogenic ★★ ⚠ same residue
CPT2 p.Pro571= Likely benign ★ same residue
CPT2 c.340+5G>A Likely pathogenic ★★ same condition
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg151Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg151Trp Pathogenic ★★ same condition
CPT2 p.Arg296Ter 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-pro571arg (accessed [today's date]).

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