Is CPT1C p.His332= (c.996C>T) pathogenic?

CPT1C p.His332= (c.996C>T) is classified Benign in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-21). Rare (popmax 0.672%, sas); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.His332= (c.996C>T)?

CPT1C p.His332= (c.996C>T) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.His332= (c.996C>T) in the general population?

CPT1C p.His332= (c.996C>T) is rare (popmax 0.672%, 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.His332=

c.996C>T · rs199774629 · VCV704317

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.672%, 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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP -11
Overall
CADD	4.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.672% South Asian · 612/91,058 alleles

Filtering AF 0.628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.61%

Overall 0.0455% 735/1,613,852 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.672%	149
Middle Eastern	0.182%	550
Remaining individualsnot grpmax-eligible	0.0688%	1,453
European (non-Finnish)	0.00542%	18,436
African / African-American	0.004%	25,007
East Asian	0.00223%	44,886
Admixed American	0.00167%	59,998

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.His332=
Coding: c.996C>T
MANE Select: NM_001199753
dbSNP: rs199774629
Type: single nucleotide variant
Location: chr19:49705940 (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-his332 (accessed [today's date]).

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