Is TECPR2 p.Ser1092= (c.3276G>A) pathogenic?

TECPR2 p.Ser1092= (c.3276G>A) is classified Likely benign in TECPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0133%, afr); Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Ser1092= (c.3276G>A)?

TECPR2 p.Ser1092= (c.3276G>A) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Ser1092= (c.3276G>A) in the general population?

TECPR2 p.Ser1092= (c.3276G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

TECPR2 p.Ser1092=

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.3276G>A · rs369793450 · VCV1897946

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.2
Overall
CADD	2.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/75,042 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00409% 66/1,614,008 alleles · ultra-rare exomes 61/1,461,768 · genomes 5/152,240 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,945
African / African-Americangrpmax	0.0133%	7,504
European (non-Finnish)	0.00364%	27,443
East Asian	0.00223%	44,882
South Asian	0.0022%	45,531
Admixed American	0.00167%	59,996

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.Ser1092=
Coding: c.3276G>A
MANE Select: NM_014844
dbSNP: rs369793450
Type: single nucleotide variant
Location: chr14:102449829 (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.Ser1092Leu Benign/Likely benign ★★ same residue
TECPR2 p.Ser1092Trp Uncertain significance ★ ⚠ same residue
TECPR2 c.1084+2T>C Likely pathogenic ★★ same condition
TECPR2 c.1418-2A>G Likely pathogenic ★★ same condition
TECPR2 c.2753-1G>A Likely pathogenic ★★ same condition
TECPR2 p.Gln1189Ter Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln191Ter Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln852Ter 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-ser1092 (accessed [today's date]).

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