Is TECPR2 p.Glu491Ter (c.1470_1471insT) pathogenic?

TECPR2 p.Glu491Ter (c.14701471insT) is classified Pathogenic in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-21). No gnomAD frequency available for this variant; Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Glu491Ter (c.1470_1471insT)?

TECPR2 p.Glu491Ter (c.1470_1471insT) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Glu491Ter (c.1470_1471insT) in the general population?

TECPR2 p.Glu491Ter (c.1470_1471insT) is no gnomAD frequency available for this variant (gnomAD).

TECPR2 p.Glu491Ter

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.1470_1471insT · rs2504423596 · VCV1943704

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.1	GERP -3.5

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.Glu491Ter
Coding: c.1470_1471insT
MANE Select: NM_014844
dbSNP: rs2504423596
Type: Insertion
Location: chr14:102434287 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 491: 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.Glu491Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
TECPR2 p.Glu491= Likely benign ★ same residue
TECPR2 c.952-15_952-14insG Likely benign ★ same condition
TECPR2 c.952-16_952-15insG Likely benign ★ same condition
TECPR2 c.952-19_952-18insG Likely benign ★ same condition
TECPR2 c.952-20_952-19insG Likely benign ★ same condition
TECPR2 c.1084+2T>C Likely pathogenic ★★ same condition
TECPR2 c.1418-2A>G 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-glu491ter (accessed [today's date]).

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