Is TECPR2 p.Ser490= (c.1470C>T) pathogenic?

TECPR2 p.Ser490= (c.1470C>T) is classified Conflicting classifications of pathogenicity in TECPR2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Rare (popmax 0.726%, afr); Associated with hereditary spastic paraplegia.

What condition is associated with TECPR2 p.Ser490= (c.1470C>T)?

TECPR2 p.Ser490= (c.1470C>T) is associated with hereditary spastic paraplegia, hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Ser490= (c.1470C>T) in the general population?

TECPR2 p.Ser490= (c.1470C>T) is rare (popmax 0.726%, afr) (gnomAD).

TECPR2 p.Ser490=

c.1470C>T · rs149584733 · VCV511253

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.726%, afr)

Conditions

hereditary spastic paraplegia

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 -7.1	GERP -3.5
Overall
CADD	1.946	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.726% African / African-American · 505/69,564 alleles

Filtering AF 0.674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.653%

Overall 0.0461% 641/1,391,190 alleles · rare exomes 298/1,238,940 · genomes 343/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.726%	138
Admixed American	0.135%	741
Remaining individualsnot grpmax-eligible	0.0647%	1,546
Middle Eastern	0.0192%	5,196
European (non-Finnish)	0.00459%	21,763
East Asian	0.00248%	40,318

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.Ser490=
Coding: c.1470C>T
MANE Select: NM_014844
dbSNP: rs149584733
Type: single nucleotide variant
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 490: the 'disordered' region

Full TECPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 49

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-ser490 (accessed [today's date]).

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