Is TECPR2 p.Ser920= (c.2760C>T) pathogenic?

TECPR2 p.Ser920= (c.2760C>T) is classified Benign in TECPR2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Ser920= (c.2760C>T)?

TECPR2 p.Ser920= (c.2760C>T) is associated with hereditary spastic paraplegia 49 (ClinVar).

TECPR2 p.Ser920=

Q: How common is TECPR2 p.Ser920= (c.2760C>T) in the general population?

TECPR2 p.Ser920= (c.2760C>T) is common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.2760C>T · rs17100923 · VCV380902

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 21.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary spastic paraplegia 49

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.6	GERP -3.6
Overall
CADD	3.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.6% African / African-American · 16,099/74,414 alleles

Filtering AF 21.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.2%

Overall 6.3% 99,852/1,584,288 alleles · common exomes 84,910/1,432,290 · genomes 14,942/151,998 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.6%	5
Finnishnot grpmax-eligible	6.47%	15
Remaining individualsnot grpmax-eligible	6.05%	17
European (non-Finnish)	6.04%	17
Admixed American	4.37%	23
Middle Eastern	3.84%	26
Ashkenazi Jewishnot grpmax-eligible	2.87%	35
South Asian	2.63%	38
Amishnot grpmax-eligible	1.54%	65
East Asian	0.0495%	2,018

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.Ser920=
Coding: c.2760C>T
MANE Select: NM_014844
dbSNP: rs17100923
Type: single nucleotide variant
Location: chr14:102443654 (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 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
TECPR2 p.Trp1024Ter Pathogenic ★★ same condition
TECPR2 p.Trp1288Ter 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-p-ser920 (accessed [today's date]).

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