Is CPT1C p.Arg579fs (c.1735_1736del) pathogenic?

CPT1C p.Arg579fs (c.17351736del) is classified Pathogenic in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). Very rare (popmax 0.00892%, eas); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Arg579fs (c.1735_1736del)?

CPT1C p.Arg579fs (c.1735_1736del) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Arg579fs (c.1735_1736del) in the general population?

CPT1C p.Arg579fs (c.1735_1736del) is very rare (popmax 0.00892%, eas) (gnomAD).

How is Autosomal dominant spastic paraplegia type 73 inherited?

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

CPT1C p.Arg579fs

c.1735_1736del · rs767517922 · VCV2733165

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,824 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00105% 17/1,612,138 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,206
South Asian	0.0044%	22,753
Remaining individualsnot grpmax-eligible	0.0016%	62,366
European (non-Finnish)	0.000679%	147,326

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: CPT1C
Protein: p.Arg579fs
Coding: c.1735_1736del
MANE Select: NM_001199753
dbSNP: rs767517922
Type: Deletion
Location: chr19:49710726 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.81 · 1 PDB

Full CPT1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 73 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant spastic paraplegia type 73 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

CPT1C p.Arg579Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
CPT1C p.Ile686fs Pathogenic ★ same condition
CPT1C p.Arg771fs Uncertain significance ★ same condition
CPT1C p.Asp726fs Uncertain significance ★ same condition
CPT1C p.Tyr702fs Uncertain significance ★ same condition
CPT1C c.1732-8del Likely benign ★ same condition
CPT1C c.1160+3A>G Uncertain significance ★★ same condition
CPT1C p.Ala117Val Uncertain significance ★★ ⚠ 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/cpt1c-p-arg579fs (accessed [today's date]).

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