Is CPT1A p.Arg89Gln (c.266G>A) pathogenic?

CPT1A p.Arg89Gln (c.266G>A) is classified Conflicting classifications of pathogenicity in CPT1A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-14). AlphaMissense: likely benign (0.0634); Ultra-rare (popmax 0.0134%, eas); Associated with carnitine palmitoyl transferase 1A deficiency.

What condition is associated with CPT1A p.Arg89Gln (c.266G>A)?

CPT1A p.Arg89Gln (c.266G>A) is associated with carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Arg89Gln (c.266G>A) in the general population?

CPT1A p.Arg89Gln (c.266G>A) is ultra-rare (popmax 0.0134%, eas) (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.Arg89Gln (c.266G>A)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

CPT1A p.Arg89Gln

c.266G>A · rs751235722 · VCV990120

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

carnitine palmitoyl transferase 1A deficiency

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.5
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.094 · regional, not allelic
Overall
CADD	14.96	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 0.0134% East Asian · 6/44,872 alleles

Filtering AF 0.00944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00911% 147/1,614,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,479
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	0.011%	9,077
South Asian	0.00329%	30,361
African / African-American	0.00133%	75,028

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.Arg89Gln
Coding: c.266G>A
MANE Select: NM_001876
dbSNP: rs751235722
Type: single nucleotide variant
Location: chr11:68812452 (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.Arg89Trp Uncertain significance ★★ ⚠ 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
CPT1A c.281+1G>A 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-arg89gln (accessed [today's date]).

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