Is CPT2 p.Gly526= (c.1578T>C) pathogenic?

CPT2 p.Gly526= (c.1578T>C) is classified Benign/Likely benign in CPT2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-04-01). Rare (popmax 0.37%, nfe); Associated with carnitine palmitoyltransferase II deficiency.

How common is CPT2 p.Gly526= (c.1578T>C) in the general population?

CPT2 p.Gly526= (c.1578T>C) is rare (popmax 0.37%, nfe) (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

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

CPT2 p.Gly526=

Q: What condition is associated with CPT2 p.Gly526= (c.1578T>C)?

CPT2 p.Gly526= (c.1578T>C) is associated with carnitine palmitoyltransferase II deficiency, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.1578T>C · rs113493395 · VCV297609

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.37%, nfe)

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.71	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -4.4	GERP -4.3
Overall
CADD	0.722	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.37% European (non-Finnish) · 4,367/1,179,278 alleles

Filtering AF 0.361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.357%

Overall 0.398% 6,414/1,612,504 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.54%	39
Remaining individualsnot grpmax-eligible	0.437%	229
European (non-Finnish)grpmax	0.37%	270
Admixed American	0.112%	893
African / African-American	0.0693%	1,442
South Asian	0.0265%	3,778
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,926
Middle Eastern	0.0165%	6,062
East Asian	0.00223%	44,816

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.Gly526=
Coding: c.1578T>C
MANE Select: NM_000098
dbSNP: rs113493395
Type: single nucleotide variant
Location: chr1:53211252 (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.Gly526Ala Uncertain significance ★ ⚠ same residue
CPT2 p.Gly526fs Likely pathogenic ★ 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-gly526 (accessed [today's date]).

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