Is TECPR2 p.Thr9fs (c.25dup) pathogenic?

TECPR2 p.Thr9fs (c.25dup) is classified Pathogenic/Likely pathogenic in TECPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-14). No gnomAD frequency available for this variant; Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Thr9fs (c.25dup)?

TECPR2 p.Thr9fs (c.25dup) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Thr9fs (c.25dup) in the general population?

TECPR2 p.Thr9fs (c.25dup) is no gnomAD frequency available for this variant (gnomAD).

TECPR2 p.Thr9fs

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.25dup · rs1486136461 · VCV1353644

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -5.6	GERP -3.1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TECPR2
Protein: p.Thr9fs
Coding: c.25dup
MANE Select: NM_014844
dbSNP: rs1486136461
Type: Duplication
Location: chr14:102376745 (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.Thr9= Likely benign ★ same residue
TECPR2 p.Thr9Ser Uncertain significance ⚠ same residue
TECPR2 p.Gln1178fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Asn44fs 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

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-thr9fs (accessed [today's date]).

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