Is CPT2 p.Arg350Cys (c.1048C>T) pathogenic?

CPT2 p.Arg350Cys (c.1048C>T) is classified Uncertain significance in CPT2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2024-11-14). AlphaMissense: ambiguous (0.439); Ultra-rare (popmax 0.0546%, afr); Associated with Inborn genetic diseases.

How common is CPT2 p.Arg350Cys (c.1048C>T) in the general population?

CPT2 p.Arg350Cys (c.1048C>T) is ultra-rare (popmax 0.0546%, afr) (gnomAD).

What do computational predictors say about CPT2 p.Arg350Cys (c.1048C>T)?

AlphaMissense predicts ambiguous (score 0.439) — an in-silico prediction, not a clinical call.

CPT2 p.Arg350Cys

Q: What condition is associated with CPT2 p.Arg350Cys (c.1048C>T)?

CPT2 p.Arg350Cys (c.1048C>T) is associated with Inborn genetic diseases, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.1048C>T · rs151003641 · VCV203662

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

ambiguous

0.439 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.439	ambiguous
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -12.41	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	27.9	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 0.0546% African / African-American · 41/75,032 alleles

Filtering AF 0.0451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0437%

Overall 0.0398% 643/1,614,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0546%	1,830
European (non-Finnish)	0.0484%	2,067
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Finnishnot grpmax-eligible	0.0187%	5,335

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.Arg350Cys
Coding: c.1048C>T
MANE Select: NM_000098
dbSNP: rs151003641
Type: single nucleotide variant
Location: chr1:53210722 (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

Inborn genetic diseases — 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 encephalopathy, acute, infection-induced, susceptibility to, 4 carnitine palmitoyltransferase II deficiency

Similar variants

CPT2 p.Arg350Gly Uncertain significance ★★ ⚠ same residue
CPT2 p.Arg350His 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-arg350cys (accessed [today's date]).

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