Is CPT1A p.Glu486Asp (c.1458G>T) pathogenic?

CPT1A p.Glu486Asp (c.1458G>T) is classified Uncertain significance in CPT1A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely pathogenic (0.819); Very rare (popmax 0.00329%, sas); Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Glu486Asp (c.1458G>T)?

CPT1A p.Glu486Asp (c.1458G>T) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Glu486Asp (c.1458G>T) in the general population?

CPT1A p.Glu486Asp (c.1458G>T) is very rare (popmax 0.00329%, 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.Glu486Asp (c.1458G>T)?

AlphaMissense predicts likely pathogenic (score 0.819) — an in-silico prediction, not a clinical call.

CPT1A p.Glu486Asp

c.1458G>T · VCV4065385

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase 1A deficiency

Computational evidence

Protein change
AlphaMissense	0.819	likely pathogenic
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -1.62	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.6	GERP 1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 46 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	29.8	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 0.00329% South Asian · 3/91,076 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,613,636 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.Glu486Asp
Coding: c.1458G>T
MANE Select: NM_001876
Type: single nucleotide variant
Location: chr11:68780640 (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 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
CPT1A c.281+1G>A Pathogenic ★★ same condition
CPT1A c.693+1G>A 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/cpt1a-p-glu486asp (accessed [today's date]).

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