Is CPT2 p.Phe383Tyr (c.1148T>A) pathogenic?

CPT2 p.Phe383Tyr (c.1148T>A) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-18). AlphaMissense: likely benign (0.3297); Ultra-rare (popmax 0.0178%, eas); Associated with CPT2-related disorder.

What condition is associated with CPT2 p.Phe383Tyr (c.1148T>A)?

CPT2 p.Phe383Tyr (c.1148T>A) is associated with CPT2-related disorder, congenital nervous system disorder, carnitine palmitoyl transferase II deficiency, myopathic form (ClinVar).

How common is CPT2 p.Phe383Tyr (c.1148T>A) in the general population?

CPT2 p.Phe383Tyr (c.1148T>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CPT2 p.Phe383Tyr (c.1148T>A)?

AlphaMissense predicts likely benign (score 0.3297) — an in-silico prediction, not a clinical call.

CPT2 p.Phe383Tyr

c.1148T>A · rs74315295 · VCV8958

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.3297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CPT2-related disorder

Computational evidence

Protein change
AlphaMissense	0.3297	likely benign ⚠ discordant with ClinVar
REVEL	0.761	pathogenic-leaning
SaProt	LLR -6.78	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	23.1	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 0.0178% East Asian · 8/44,886 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000558% 9/1,614,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
African / African-American	0.00133%	74,914

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.Phe383Tyr
Coding: c.1148T>A
MANE Select: NM_000098
dbSNP: rs74315295
Type: single nucleotide variant
Location: chr1:53210822 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 383: a UniProt-annotated variant site (in cpt2d; hepatocardiomuscular form)

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CPT2-related disorder

Also linked: congenital nervous system disorder 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 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
CPT2 p.Arg151Trp 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-phe383tyr (accessed [today's date]).

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