Is CPT1C p.Val541= (c.1623C>T) pathogenic?

CPT1C p.Val541= (c.1623C>T) is classified Likely benign in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). Very rare (popmax 0.00769%, sas); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Val541= (c.1623C>T)?

CPT1C p.Val541= (c.1623C>T) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Val541= (c.1623C>T) in the general population?

CPT1C p.Val541= (c.1623C>T) is very rare (popmax 0.00769%, 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.Val541=

c.1623C>T · rs377075105 · VCV719258

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

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	Δ0.36	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -11
Overall
CADD	8.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,076 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00223% 36/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,011
European (non-Finnish)	0.00237%	42,144
African / African-American	0.00133%	74,930

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.Val541=
Coding: c.1623C>T
MANE Select: NM_001199753
dbSNP: rs377075105
Type: single nucleotide variant
Location: chr19:49710376 (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.Val541Ala 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-val541 (accessed [today's date]).

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