Is CPT1C p.Ser131Pro (c.391T>C) pathogenic?

CPT1C p.Ser131Pro (c.391T>C) is classified Uncertain significance in CPT1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.703); Very rare (popmax 0.000339%, nfe); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Ser131Pro (c.391T>C)?

CPT1C p.Ser131Pro (c.391T>C) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Ser131Pro (c.391T>C) in the general population?

CPT1C p.Ser131Pro (c.391T>C) is very rare (popmax 0.000339%, nfe) (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.Ser131Pro (c.391T>C)?

AlphaMissense predicts likely pathogenic (score 0.703) — an in-silico prediction, not a clinical call.

CPT1C p.Ser131Pro

c.391T>C · rs2082971645 · VCV2718104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
AlphaMissense	0.703	likely pathogenic
REVEL	0.656	pathogenic-leaning
SaProt	LLR -13.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.77 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,354 alleles · very rare

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.Ser131Pro
Coding: c.391T>C
MANE Select: NM_001199753
dbSNP: rs2082971645
Type: single nucleotide variant
Location: chr19:49700793 (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.Ser131Tyr Uncertain significance ★ ⚠ same residue
CPT1C p.Ser131= Likely benign ★ 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-ser131pro (accessed [today's date]).

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