Is CPT2 p.Thr589Met (c.1766C>T) pathogenic?

CPT2 p.Thr589Met (c.1766C>T) is classified Uncertain significance in CPT2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.8747); Very rare (popmax 0.00223%, eas); Associated with carnitine palmitoyl transferase II deficiency, neonatal form.

What condition is associated with CPT2 p.Thr589Met (c.1766C>T)?

CPT2 p.Thr589Met (c.1766C>T) is associated with carnitine palmitoyl transferase II deficiency, neonatal form, myopathy, carnitine palmitoyl transferase II deficiency, myopathic form (ClinVar).

How common is CPT2 p.Thr589Met (c.1766C>T) in the general population?

CPT2 p.Thr589Met (c.1766C>T) 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.Thr589Met (c.1766C>T)?

AlphaMissense predicts likely pathogenic (score 0.8747) — an in-silico prediction, not a clinical call.

CPT2 p.Thr589Met

c.1766C>T · rs756414686 · VCV804352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase II deficiency, neonatal form

Computational evidence

Protein change
AlphaMissense	0.8747	likely pathogenic
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -14.94	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	25.9	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

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000342% 5/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
Admixed American	0.00167%	60,020
African / African-American	0.00133%	75,060
European (non-Finnish)	0.000169%	590,023

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.Thr589Met
Coding: c.1766C>T
MANE Select: NM_000098
dbSNP: rs756414686
Type: single nucleotide variant
Location: chr1:53213384 (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

Also linked: myopathy carnitine palmitoyl transferase II deficiency, myopathic form carnitine palmitoyl transferase II deficiency, severe infantile form encephalopathy, acute, infection-induced, susceptibility to, 4

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Thr589= Benign/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.Ala67Gly Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Gln 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

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-thr589met (accessed [today's date]).

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