Is CPT1C p.Ala628Pro (c.1882G>C) pathogenic?

CPT1C p.Ala628Pro (c.1882G>C) is classified Uncertain significance in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-06). AlphaMissense: likely benign (0.3271); Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Ala628Pro (c.1882G>C)?

CPT1C p.Ala628Pro (c.1882G>C) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Ala628Pro (c.1882G>C) in the general population?

CPT1C p.Ala628Pro (c.1882G>C) is absent from gnomAD v4.1 (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.Ala628Pro (c.1882G>C)?

AlphaMissense predicts likely benign (score 0.3271) — an in-silico prediction, not a clinical call.

CPT1C p.Ala628Pro

c.1882G>C · rs774619970 · VCV1473433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3271 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
AlphaMissense	0.3271	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	phastCons 0.2
Regional constraint	o/e 0.87	unconstrained · MANE · 4,824 bp · p 0.0093 · regional, not allelic
Overall
CADD	20.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPT1C
Protein: p.Ala628Pro
Coding: c.1882G>C
MANE Select: NM_001199753
dbSNP: rs774619970
Type: single nucleotide variant
Location: chr19:49711824 (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-ala628pro (accessed [today's date]).

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