Is CPT2 p.Thr589= (c.1767G>A) pathogenic?

CPT2 p.Thr589= (c.1767G>A) is classified Benign/Likely benign in CPT2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.49%, afr); Associated with carnitine palmitoyltransferase II deficiency.

How common is CPT2 p.Thr589= (c.1767G>A) in the general population?

CPT2 p.Thr589= (c.1767G>A) is low-frequency (popmax 2.49%, afr) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CPT2 p.Thr589=

Q: What condition is associated with CPT2 p.Thr589= (c.1767G>A)?

CPT2 p.Thr589= (c.1767G>A) is associated with carnitine palmitoyltransferase II deficiency, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.1767G>A · rs77565483 · VCV92432

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.49%, afr)

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -4.8
Overall
CADD	0.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.49% African / African-American · 1,867/75,044 alleles

Filtering AF 2.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.329% 5,314/1,614,210 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.49%	40
Middle Eastern	1.4%	71
Admixed American	0.975%	103
Ashkenazi Jewishnot grpmax-eligible	0.821%	122
Remaining individualsnot grpmax-eligible	0.656%	152
European (non-Finnish)	0.174%	574
Finnishnot grpmax-eligible	0.064%	1,562
South Asian	0.0274%	3,643
East Asian	0.00223%	44,886

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.Thr589=
Coding: c.1767G>A
MANE Select: NM_000098
dbSNP: rs77565483
Type: single nucleotide variant
Location: chr1:53213385 (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 palmitoyltransferase II deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Thr589Met Uncertain significance ★★ ⚠ 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
CPT2 p.Arg151Gln 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-thr589 (accessed [today's date]).

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