Is TECPR2 p.Pro439Ser (c.1315C>T) pathogenic?

TECPR2 p.Pro439Ser (c.1315C>T) is classified Benign in TECPR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0754); Common (popmax 5.66%, amr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Pro439Ser (c.1315C>T)?

TECPR2 p.Pro439Ser (c.1315C>T) is associated with hereditary spastic paraplegia 49, hereditary spastic paraplegia (ClinVar).

What do computational predictors say about TECPR2 p.Pro439Ser (c.1315C>T)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

TECPR2 p.Pro439Ser

Q: How common is TECPR2 p.Pro439Ser (c.1315C>T) in the general population?

TECPR2 p.Pro439Ser (c.1315C>T) is common (popmax 5.66%, amr) — 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.1315C>T · rs2273906 · VCV380927

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.66%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 49

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP 1.8, phastCons 0.3
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	4.053	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.66% Admixed American · 3,393/59,976 alleles

Filtering AF 5.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.43%

Overall 3.44% 55,480/1,612,818 alleles · common exomes 49,130/1,460,508 · genomes 6,350/152,310 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	5.66%	18
African / African-American	5.59%	18
Middle Eastern	5.49%	18
Amishnot grpmax-eligible	4.93%	20
Ashkenazi Jewishnot grpmax-eligible	4.68%	21
East Asian	3.94%	25
Finnishnot grpmax-eligible	3.94%	25
South Asian	3.83%	26
Remaining individualsnot grpmax-eligible	3.61%	28
European (non-Finnish)	3.06%	33

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.Pro439Ser
Coding: c.1315C>T
MANE Select: NM_014844
dbSNP: rs2273906
Type: single nucleotide variant
Location: chr14:102432026 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 439: the 'disordered' region; a UniProt-annotated variant site (in)

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.Pro439Leu Uncertain significance ★ ⚠ same residue
TECPR2 p.Pro439= Likely benign ★ 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-pro439ser (accessed [today's date]).

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