Is CPT2 p.Ala67Gly (c.200C>G) pathogenic?

CPT2 p.Ala67Gly (c.200C>G) is classified Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-02). AlphaMissense: likely benign (0.3037); Very rare (popmax 0.0089%, nfe); Associated with encephalopathy, acute, infection-induced, susceptibility to, 4.

What condition is associated with CPT2 p.Ala67Gly (c.200C>G)?

CPT2 p.Ala67Gly (c.200C>G) is associated with encephalopathy, acute, infection-induced, susceptibility to, 4, carnitine palmitoyl transferase II deficiency, severe infantile form, carnitine palmitoyltransferase II deficiency (ClinVar).

How common is CPT2 p.Ala67Gly (c.200C>G) in the general population?

CPT2 p.Ala67Gly (c.200C>G) is very rare (popmax 0.0089%, nfe) (gnomAD).

What do computational predictors say about CPT2 p.Ala67Gly (c.200C>G)?

AlphaMissense predicts likely benign (score 0.3037) — an in-silico prediction, not a clinical call.

CPT2 p.Ala67Gly

c.200C>G · rs201966320 · VCV851878

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.3037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

encephalopathy, acute, infection-induced, susceptibility to, 4

Computational evidence

Protein change
AlphaMissense	0.3037	likely benign ⚠ discordant with ClinVar
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -9.10	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	26.0	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 0.0089% European (non-Finnish) · 105/1,179,942 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00669% 108/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0089%	11,238
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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.Ala67Gly
Coding: c.200C>G
MANE Select: NM_000098
dbSNP: rs201966320
Type: single nucleotide variant
Location: chr1:53200766 (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

encephalopathy, acute, infection-induced, susceptibility to, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyl transferase II deficiency, severe infantile form carnitine palmitoyltransferase II deficiency

Similar variants

CPT2 p.Ala67= 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.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-ala67gly (accessed [today's date]).

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