Is CPT2 p.Val533Ala (c.1598T>C) pathogenic?

CPT2 p.Val533Ala (c.1598T>C) is classified Conflicting classifications of pathogenicity in CPT2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0493); Rare (popmax 0.76%, afr); Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Val533Ala (c.1598T>C)?

CPT2 p.Val533Ala (c.1598T>C) is associated with carnitine palmitoyltransferase II deficiency (ClinVar).

How common is CPT2 p.Val533Ala (c.1598T>C) in the general population?

CPT2 p.Val533Ala (c.1598T>C) is rare (popmax 0.76%, afr) (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.Val533Ala (c.1598T>C)?

AlphaMissense predicts likely benign (score 0.0493) — an in-silico prediction, not a clinical call.

CPT2 p.Val533Ala

c.1598T>C · rs144703247 · VCV203657

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0493 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.76%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
AlphaMissense	0.0493	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -4.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.39	GERP -2.2, phastCons 0.025
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	1.13	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 0.76% African / African-American · 570/74,972 alleles

Filtering AF 0.709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.688%

Overall 0.0403% 650/1,611,954 alleles · rare exomes 323/1,459,684 · genomes 327/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.76%	132
Admixed American	0.0569%	1,757
Remaining individualsnot grpmax-eligible	0.0385%	2,601
Middle Eastern	0.033%	3,029
European (non-Finnish)	0.0017%	58,952

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.Val533Ala
Coding: c.1598T>C
MANE Select: NM_000098
dbSNP: rs144703247
Type: single nucleotide variant
Location: chr1:53211272 (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

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Val533= 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.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-val533ala (accessed [today's date]).

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