Is TECPR2 c.222delG pathogenic?

TECPR2 c.222delG is classified Pathogenic/Likely pathogenic in TECPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-10). Very rare (popmax 0.000171%, nfe); Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 c.222delG?

TECPR2 c.222delG is associated with hereditary spastic paraplegia 49, hereditary spastic paraplegia (ClinVar).

How common is TECPR2 c.222delG in the general population?

TECPR2 c.222delG is very rare (popmax 0.000171%, nfe) (gnomAD).

TECPR2 c.222delG

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.

rs1567327482 · VCV1454429

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Non-coding constraint	Z 1.83	1 kb window · o/e 0.88 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,172,736 alleles

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

Overall 0.000125% 2/1,595,058 alleles · very rare exomes 2/1,442,768 · genomes 0/152,290 · joint denominator

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
Coding: c.222delG
MANE Select: NM_014844
dbSNP: rs1567327482
Type: Deletion
Location: chr14:102407337 (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

Also linked: hereditary spastic paraplegia

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

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

TECPR2 p.Asn1277fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Asn944fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Asp259fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln1263fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gly584fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Leu1139fs Pathogenic ★★ same condition
TECPR2 p.Leu440fs Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Lys343fs 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-c-222delg (accessed [today's date]).

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