Is TECPR2 p.Leu863= (c.2589C>A) pathogenic?

TECPR2 p.Leu863= (c.2589C>A) is classified Likely benign in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-30). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Leu863= (c.2589C>A)?

TECPR2 p.Leu863= (c.2589C>A) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Leu863= (c.2589C>A) in the general population?

TECPR2 p.Leu863= (c.2589C>A) is absent from gnomAD v4.1 (gnomAD).

TECPR2 p.Leu863=

Q: How is Hereditary sensory and autonomic neuropathy due to TECPR2 mutation inherited?

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

c.2589C>A · rs1382296444 · VCV2860770

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 49

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.009	GERP -0.13, phastCons 0.8
Overall
CADD	4.542	PHRED · no single calibrated threshold — expert panels disagree

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: TECPR2
Protein: p.Leu863=
Coding: c.2589C>A
MANE Select: NM_014844
dbSNP: rs1382296444
Type: single nucleotide variant
Location: chr14:102440446 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27

Full TECPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 49 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary sensory and autonomic neuropathy due to TECPR2 mutation (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

TECPR2 c.1084+2T>C Likely pathogenic ★★ same condition
TECPR2 c.1418-2A>G Likely pathogenic ★★ same condition
TECPR2 c.2753-1G>A Likely pathogenic ★★ same condition
TECPR2 p.Gln1189Ter Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln191Ter Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln852Ter Pathogenic ★★ same condition
TECPR2 p.Trp1024Ter Pathogenic ★★ same condition
TECPR2 p.Trp1288Ter Pathogenic/Likely pathogenic ★★ 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/tecpr2-p-leu863 (accessed [today's date]).

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