Is CPT1A p.Arg201Trp (c.601C>T) pathogenic?

CPT1A p.Arg201Trp (c.601C>T) is classified Uncertain significance in CPT1A (ClinVar, Single submitter, 2 submitters; last evaluated 2021-10-29). AlphaMissense: likely benign (0.2319); Ultra-rare (popmax 0.0845%, sas); Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Arg201Trp (c.601C>T)?

CPT1A p.Arg201Trp (c.601C>T) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Arg201Trp (c.601C>T) in the general population?

CPT1A p.Arg201Trp (c.601C>T) is ultra-rare (popmax 0.0845%, sas) (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.Arg201Trp (c.601C>T)?

AlphaMissense predicts likely benign (score 0.2319) — an in-silico prediction, not a clinical call.

CPT1A p.Arg201Trp

c.601C>T · rs373344573 · VCV1046460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2319 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0845%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase 1A deficiency

Computational evidence

Protein change
AlphaMissense	0.2319	likely benign
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -12.93	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 4.7	GERP 0.67, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 46 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	26.1	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 0.0845% South Asian · 77/91,080 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00545% 88/1,613,896 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0845%	1,183
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0064%	15,625
East Asian	0.00446%	22,438
African / African-American	0.00133%	75,010
European (non-Finnish)	0.00017%	589,943

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.Arg201Trp
Coding: c.601C>T
MANE Select: NM_001876
dbSNP: rs373344573
Type: single nucleotide variant
Location: chr11:68799310 (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.Arg201Gln Uncertain significance ★★ ⚠ same residue
CPT1A p.Arg201= 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-arg201trp (accessed [today's date]).

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