Is CPT1C p.Pro247= (c.741G>A) pathogenic?

CPT1C p.Pro247= (c.741G>A) is classified Likely benign in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.00878%, sas); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Pro247= (c.741G>A)?

CPT1C p.Pro247= (c.741G>A) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Pro247= (c.741G>A) in the general population?

CPT1C p.Pro247= (c.741G>A) is very rare (popmax 0.00878%, sas) (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.Pro247=

c.741G>A · rs750408494 · VCV2140883

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4
Overall
CADD	6.917	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,074 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00223% 36/1,613,866 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
African / African-American	0.00267%	37,430
East Asian	0.00223%	44,894
European (non-Finnish)	0.00203%	49,166
Admixed American	0.00167%	59,970

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.Pro247=
Coding: c.741G>A
MANE Select: NM_001199753
dbSNP: rs750408494
Type: single nucleotide variant
Location: chr19:49704757 (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.Pro247Leu Uncertain significance ★★ ⚠ same residue
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

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-pro247 (accessed [today's date]).

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