Is CPT1A p.Arg595Trp (c.1783C>T) pathogenic?

CPT1A p.Arg595Trp (c.1783C>T) is classified Likely pathogenic in CPT1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). AlphaMissense: likely pathogenic (0.963); Very rare (popmax 0.000424%, nfe); Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Arg595Trp (c.1783C>T)?

CPT1A p.Arg595Trp (c.1783C>T) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Arg595Trp (c.1783C>T) in the general population?

CPT1A p.Arg595Trp (c.1783C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Carnitine palmitoyl transferase 1A deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CPT1A p.Arg595Trp (c.1783C>T)?

AlphaMissense predicts likely pathogenic (score 0.963) — an in-silico prediction, not a clinical call.

CPT1A p.Arg595Trp

c.1783C>T · rs576663980 · VCV2735690

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase 1A deficiency

Computational evidence

Protein change
AlphaMissense	0.963	likely pathogenic ✓ concordant with ClinVar
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -16.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.093, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 46 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	33.0	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 0.000424% European (non-Finnish) · 5/1,180,034 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,746 alleles · very rare

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: CPT1A
Protein: p.Arg595Trp
Coding: c.1783C>T
MANE Select: NM_001876
dbSNP: rs576663980
Type: single nucleotide variant
Location: chr11:68762719 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.55 · 1 PDB

Full CPT1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

carnitine palmitoyl transferase 1A deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Carnitine palmitoyl transferase 1A deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CPT1A p.Arg595Gln Uncertain significance ★★ ⚠ same residue
CPT1A p.Arg595= Likely benign ★ same residue
CPT1A c.1163+1G>A Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.1163+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPT1A c.1352+1G>C Likely pathogenic ★★ same condition
CPT1A c.1459-1G>A Likely pathogenic ★★ same condition
CPT1A c.1575+1G>T Likely pathogenic ★★ same condition
CPT1A c.2028+2T>G 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/cpt1a-p-arg595trp (accessed [today's date]).

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