Is TECPR2 p.Asn44fs (c.129dup) pathogenic?

TECPR2 p.Asn44fs (c.129dup) is classified Likely pathogenic in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Asn44fs (c.129dup)?

TECPR2 p.Asn44fs (c.129dup) is associated with hereditary spastic paraplegia 49 (ClinVar).

TECPR2 p.Asn44fs

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.129dup · VCV4815739

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 2 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.49	GERP -3.3, phastCons 0.001

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

Variant & gene context

Gene: TECPR2
Protein: p.Asn44fs
Coding: c.129dup
MANE Select: NM_014844
Type: Duplication
Location: chr14:102376848 (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 p.Asn44= Likely benign ★ same residue
TECPR2 p.Gln1178fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Thr9fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.His376fs Likely pathogenic ★ same condition
TECPR2 p.Leu1210fs Pathogenic ★ same condition
TECPR2 p.Ser520delinsValSerTrpAlaValAlaTrpIleSerTer Pathogenic ★ same condition
TECPR2 p.Thr232fs Likely pathogenic ★ same condition
TECPR2 p.Thr917fs 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-asn44fs (accessed [today's date]).

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