Is CPT1C p.Ala407Val (c.1220C>T) pathogenic?

CPT1C p.Ala407Val (c.1220C>T) is classified Benign in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). AlphaMissense: likely benign (0.1125); Rare (popmax 0.339%, afr); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Ala407Val (c.1220C>T)?

CPT1C p.Ala407Val (c.1220C>T) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Ala407Val (c.1220C>T) in the general population?

CPT1C p.Ala407Val (c.1220C>T) is rare (popmax 0.339%, afr) (gnomAD).

How is Autosomal dominant spastic paraplegia type 73 inherited?

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

What do computational predictors say about CPT1C p.Ala407Val (c.1220C>T)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

CPT1C p.Ala407Val

c.1220C>T · rs61748956 · VCV1980532

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.339%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -8.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	phastCons 0.96
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.77 · regional, not allelic
Overall
CADD	18.74	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.339% African / African-American · 240/70,716 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.291%

Overall 0.0184% 282/1,536,460 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.339%	295
Remaining individualsnot grpmax-eligible	0.0273%	3,662
Middle Eastern	0.0174%	5,736
Admixed American	0.016%	6,254
South Asian	0.00982%	10,179
East Asian	0.00482%	20,730
European (non-Finnish)	0.000699%	143,162

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.Ala407Val
Coding: c.1220C>T
MANE Select: NM_001199753
dbSNP: rs61748956
Type: single nucleotide variant
Location: chr19:49706290 (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.Ala407= Likely benign ★ same residue
CPT1C p.Ala407Glu 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

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-ala407val (accessed [today's date]).

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