Is CPT2 p.Pro41Leu (c.122C>T) pathogenic?

CPT2 p.Pro41Leu (c.122C>T) is classified Uncertain significance in CPT2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-04-11). AlphaMissense: likely pathogenic (0.6836); Very rare (popmax 0.00166%, nfe); Associated with encephalopathy, acute, infection-induced, susceptibility to, 4.

What condition is associated with CPT2 p.Pro41Leu (c.122C>T)?

CPT2 p.Pro41Leu (c.122C>T) is associated with encephalopathy, acute, infection-induced, susceptibility to, 4, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

How common is CPT2 p.Pro41Leu (c.122C>T) in the general population?

CPT2 p.Pro41Leu (c.122C>T) is very rare (popmax 0.00166%, nfe) (gnomAD).

What do computational predictors say about CPT2 p.Pro41Leu (c.122C>T)?

AlphaMissense predicts likely pathogenic (score 0.6836) — an in-silico prediction, not a clinical call.

CPT2 p.Pro41Leu

c.122C>T · rs760976212 · VCV1200879

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.6836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00166%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.6836	likely pathogenic
REVEL	0.584	indeterminate
SaProt	LLR -13.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	28.7	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

Grpmax group 0.00166% European (non-Finnish) · 19/1,146,472 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000854%

Overall 0.00123% 19/1,539,286 alleles · very rare

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.Pro41Leu
Coding: c.122C>T
MANE Select: NM_000098
dbSNP: rs760976212
Type: single nucleotide variant
Location: chr1:53197065 (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, myopathic form carnitine palmitoyl transferase II deficiency, severe infantile form carnitine palmitoyl transferase II deficiency, neonatal form carnitine palmitoyltransferase II deficiency

Similar variants

CPT2 p.Pro41His Uncertain significance ★ ⚠ same residue
CPT2 p.Pro41= Likely benign ★ same residue
CPT2 p.Pro41_Met43del 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

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-pro41leu (accessed [today's date]).

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