Is CPT2 p.Arg193Cys (c.577C>T) pathogenic?

CPT2 p.Arg193Cys (c.577C>T) is classified Conflicting classifications of pathogenicity in CPT2 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.2074); Rare (popmax 0.136%, sas); Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Arg193Cys (c.577C>T)?

CPT2 p.Arg193Cys (c.577C>T) is associated with carnitine palmitoyltransferase II deficiency (ClinVar).

How common is CPT2 p.Arg193Cys (c.577C>T) in the general population?

CPT2 p.Arg193Cys (c.577C>T) is rare (popmax 0.136%, sas) (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.Arg193Cys (c.577C>T)?

AlphaMissense predicts likely benign (score 0.2074) — an in-silico prediction, not a clinical call.

CPT2 p.Arg193Cys

c.577C>T · rs375968699 · VCV287483

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.2074 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
AlphaMissense	0.2074	likely benign
REVEL	0.751	pathogenic-leaning
SaProt	LLR -11.46	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	26.8	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 0.136% South Asian · 124/91,082 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.0158% 255/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.136%	735
East Asian	0.0958%	1,044
Remaining individualsnot grpmax-eligible	0.0608%	1,645
African / African-American	0.0386%	2,588
Admixed American	0.005%	20,004
European (non-Finnish)	0.00153%	65,557

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.Arg193Cys
Coding: c.577C>T
MANE Select: NM_000098
dbSNP: rs375968699
Type: single nucleotide variant
Location: chr1:53210251 (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.Arg193His Uncertain significance ★★ ⚠ same residue
CPT2 p.Arg193Gly 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-arg193cys (accessed [today's date]).

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