Is CPT2 p.Thr150Ala (c.448A>G) pathogenic?

CPT2 p.Thr150Ala (c.448A>G) is classified Conflicting classifications of pathogenicity in CPT2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0858); Ultra-rare (popmax 0.0569%, nfe); Associated with carnitine palmitoyl transferase II deficiency, severe infantile form.

How common is CPT2 p.Thr150Ala (c.448A>G) in the general population?

CPT2 p.Thr150Ala (c.448A>G) is ultra-rare (popmax 0.0569%, nfe) (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.Thr150Ala (c.448A>G)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

CPT2 p.Thr150Ala

Q: What condition is associated with CPT2 p.Thr150Ala (c.448A>G)?

CPT2 p.Thr150Ala (c.448A>G) is associated with carnitine palmitoyl transferase II deficiency, severe infantile form, carnitine palmitoyltransferase II deficiency (ClinVar).

c.448A>G · rs141505320 · VCV374947

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0569%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

carnitine palmitoyl transferase II deficiency, severe infantile form

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2.4, phastCons 0.98
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	22.3	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 0.0569% European (non-Finnish) · 671/1,179,998 alleles

Filtering AF 0.0533% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0519%

Overall 0.0431% 696/1,613,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0569%	1,759
Remaining individualsnot grpmax-eligible	0.0336%	2,975
African / African-American	0.00401%	24,959
Admixed American	0.00167%	59,990

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.Thr150Ala
Coding: c.448A>G
MANE Select: NM_000098
dbSNP: rs141505320
Type: single nucleotide variant
Location: chr1:53210122 (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, severe infantile form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyltransferase II deficiency

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Thr150Pro Uncertain significance ★ ⚠ same residue
CPT2 p.Thr150Ser 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

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-thr150ala (accessed [today's date]).

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