Is CPT1C p.Thr52= (c.156C>T) pathogenic?

CPT1C p.Thr52= (c.156C>T) is classified Likely benign in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). Ultra-rare (popmax 0.01%, amr); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Thr52= (c.156C>T)?

CPT1C p.Thr52= (c.156C>T) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Thr52= (c.156C>T) in the general population?

CPT1C p.Thr52= (c.156C>T) is ultra-rare (popmax 0.01%, amr) (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.Thr52=

c.156C>T · rs149279870 · VCV707514

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -9.2
Overall
CADD	12.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,000 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00427% 69/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
European (non-Finnish)	0.00466%	21,455
African / African-American	0.004%	25,018
East Asian	0.00223%	44,864
Remaining individualsnot grpmax-eligible	0.0016%	62,502
South Asian	0.0011%	91,076

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.Thr52=
Coding: c.156C>T
MANE Select: NM_001199753
dbSNP: rs149279870
Type: single nucleotide variant
Location: chr19:49697340 (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 c.1160+3A>G Uncertain significance ★★ same condition
CPT1C p.Ala117Val Uncertain significance ★★ ⚠ same condition
CPT1C p.Ala19Thr Uncertain significance ★★ ⚠ same condition
CPT1C p.Ala203Thr Uncertain significance ★★ ⚠ same condition
CPT1C p.Ala401Val Uncertain significance ★★ ⚠ same condition
CPT1C p.Ala422Thr Uncertain significance ★★ ⚠ same condition
CPT1C p.Ala431Val Uncertain significance ★★ ⚠ same condition
CPT1C p.Ala4Glu 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-thr52 (accessed [today's date]).

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