Is TECPR2 p.Pro601Leu (c.1802C>T) pathogenic?

TECPR2 p.Pro601Leu (c.1802C>T) is classified Benign in TECPR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0751); Low-frequency (popmax 2.27%, amr); Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Pro601Leu (c.1802C>T)?

TECPR2 p.Pro601Leu (c.1802C>T) is associated with hereditary spastic paraplegia 49, hereditary spastic paraplegia (ClinVar).

How common is TECPR2 p.Pro601Leu (c.1802C>T) in the general population?

TECPR2 p.Pro601Leu (c.1802C>T) is low-frequency (popmax 2.27%, amr) (gnomAD).

What do computational predictors say about TECPR2 p.Pro601Leu (c.1802C>T)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

TECPR2 p.Pro601Leu

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.1802C>T · rs118141823 · VCV220729

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.27%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 49

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.82	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 -0.26	GERP -3
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	5.5	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 2.27% Admixed American · 1,329/58,614 alleles

Filtering AF 2.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.16%

Overall 1.94% 30,777/1,583,794 alleles · low-frequency exomes 28,271/1,431,522 · genomes 2,506/152,272 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	5.59%	18
Ashkenazi Jewishnot grpmax-eligible	3.25%	31
Admixed Americangrpmax	2.27%	44
European (non-Finnish)	2.19%	46
Remaining individualsnot grpmax-eligible	1.97%	51
Finnishnot grpmax-eligible	1.36%	73
South Asian	0.832%	120
Middle Eastern	0.421%	238
African / African-American	0.378%	265
East Asian	0.00225%	44,482

Amish 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.Pro601Leu
Coding: c.1802C>T
MANE Select: NM_014844
dbSNP: rs118141823
Type: single nucleotide variant
Location: chr14:102434619 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 601: 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

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.Pro601= 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
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-pro601leu (accessed [today's date]).

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