Is TECPR2 p.Thr387fs (c.1160_1161del) pathogenic?

TECPR2 p.Thr387fs (c.11601161del) is classified Pathogenic in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.000171%, nfe); Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Thr387fs (c.1160_1161del)?

TECPR2 p.Thr387fs (c.1160_1161del) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Thr387fs (c.1160_1161del) in the general population?

TECPR2 p.Thr387fs (c.1160_1161del) is very rare (popmax 0.000171%, nfe) (gnomAD).

TECPR2 p.Thr387fs

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.1160_1161del · rs1213755599 · VCV1071450

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Conditions

hereditary spastic paraplegia 49

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 0.62, phastCons 0.001
Overall
CADD	18.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,171,162 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,603,254 alleles · very rare exomes 2/1,451,022 · genomes 1/152,232 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,884
European (non-Finnish)grpmax	0.000171%	585,580

Remaining individuals 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: TECPR2
Protein: p.Thr387fs
Coding: c.1160_1161del
MANE Select: NM_014844
dbSNP: rs1213755599
Type: Microsatellite
Location: chr14:102431869 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 387: the 'disordered' region

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 p.Thr387= Likely benign ★ same residue
TECPR2 p.Glu12fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Leu225_Cys226insTer Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Thr649fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Lys471del Uncertain significance ★★ same condition
TECPR2 c.2578+10CCCGCTCCCTGCT[3] Likely benign ★★ same condition
TECPR2 c.2578+30_2578+42del Benign ★★ same condition
TECPR2 p.Lys471dup Likely benign ★★ 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-thr387fs (accessed [today's date]).

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