Is TECPR2 p.Ser506= (c.1518G>A) pathogenic?

TECPR2 p.Ser506= (c.1518G>A) is classified Likely benign in TECPR2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-26). Ultra-rare (popmax 0.0722%, eas); Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Ser506= (c.1518G>A)?

TECPR2 p.Ser506= (c.1518G>A) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Ser506= (c.1518G>A) in the general population?

TECPR2 p.Ser506= (c.1518G>A) is ultra-rare (popmax 0.0722%, eas) (gnomAD).

TECPR2 p.Ser506=

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.1518G>A · rs370643085 · VCV729469

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0722%, eas)

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 -1.7	GERP -1.6
Overall
CADD	4.637	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0722% East Asian · 31/42,938 alleles

Filtering AF 0.0522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0454%

Overall 0.00376% 55/1,462,654 alleles · ultra-rare exomes 49/1,310,512 · genomes 6/152,142 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0722%	1,385
African / African-American	0.00844%	11,851
South Asian	0.00836%	11,966
Remaining individualsnot grpmax-eligible	0.00536%	18,657
Admixed American	0.00475%	21,074
European (non-Finnish)	0.000725%	138,005

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.Ser506=
Coding: c.1518G>A
MANE Select: NM_014844
dbSNP: rs370643085
Type: single nucleotide variant
Location: chr14:102434335 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 506: 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.Ser506Leu 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
TECPR2 p.Trp1024Ter 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-ser506 (accessed [today's date]).

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