Is CPT1C p.Arg285= (c.855C>T) pathogenic?

CPT1C p.Arg285= (c.855C>T) is classified Conflicting classifications of pathogenicity in CPT1C (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-23). Ultra-rare (popmax 0.0659%, mid); Associated with hereditary spastic paraplegia 73.

What condition is associated with CPT1C p.Arg285= (c.855C>T)?

CPT1C p.Arg285= (c.855C>T) is associated with hereditary spastic paraplegia 73 (ClinVar).

How common is CPT1C p.Arg285= (c.855C>T) in the general population?

CPT1C p.Arg285= (c.855C>T) is ultra-rare (popmax 0.0659%, mid) (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.Arg285=

c.855C>T · rs140099471 · VCV444480

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, mid)

Conditions

hereditary spastic paraplegia 73

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62
Overall
CADD	5.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% Middle Eastern · 4/6,068 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0172% 277/1,613,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.54%	185
Middle Easterngrpmax	0.0659%	1,517
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Admixed American	0.0117%	8,567
South Asian	0.00768%	13,013
European (non-Finnish)	0.00517%	19,344
Finnishnot grpmax-eligible	0.00312%	32,010

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg285=
Coding: c.855C>T
MANE Select: NM_001199753
dbSNP: rs140099471
Type: single nucleotide variant
Location: chr19:49705090 (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.Arg285His 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-arg285 (accessed [today's date]).

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