Is CPT1A p.Pro59Ser (c.175C>T) pathogenic?

CPT1A p.Pro59Ser (c.175C>T) is classified Uncertain significance in CPT1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-07). AlphaMissense: likely pathogenic (0.6108); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with CPT1A p.Pro59Ser (c.175C>T)?

CPT1A p.Pro59Ser (c.175C>T) is associated with Inborn genetic diseases, carnitine palmitoyl transferase 1A deficiency (ClinVar).

How common is CPT1A p.Pro59Ser (c.175C>T) in the general population?

CPT1A p.Pro59Ser (c.175C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CPT1A p.Pro59Ser (c.175C>T)?

AlphaMissense predicts likely pathogenic (score 0.6108) — an in-silico prediction, not a clinical call.

CPT1A p.Pro59Ser

c.175C>T · rs780084139 · VCV2547837

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6108	likely pathogenic
REVEL	0.687	pathogenic-leaning
SaProt	LLR -13.59	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.094 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,878 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000205% 3/1,461,894 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.Pro59Ser
Coding: c.175C>T
MANE Select: NM_001876
dbSNP: rs780084139
Type: single nucleotide variant
Location: chr11:68812543 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: carnitine palmitoyl transferase 1A deficiency

Similar variants

CPT1A p.Pro59Leu 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-pro59ser (accessed [today's date]).

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