Is TECPR2 p.Ala604Val (c.1811C>T) pathogenic?

TECPR2 p.Ala604Val (c.1811C>T) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely benign (0.0751); Very rare (popmax 0.000515%, nfe); Associated with hereditary spastic paraplegia 49.

What condition is associated with TECPR2 p.Ala604Val (c.1811C>T)?

TECPR2 p.Ala604Val (c.1811C>T) is associated with hereditary spastic paraplegia 49 (ClinVar).

How common is TECPR2 p.Ala604Val (c.1811C>T) in the general population?

TECPR2 p.Ala604Val (c.1811C>T) is very rare (popmax 0.000515%, nfe) (gnomAD).

What do computational predictors say about TECPR2 p.Ala604Val (c.1811C>T)?

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

TECPR2 p.Ala604Val

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.1811C>T · rs1060502180 · VCV408912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000515%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 49

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.49	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 -5.9	GERP -3.5
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	0.021	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000515% European (non-Finnish) · 6/1,164,960 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000377% 6/1,590,922 alleles · very rare exomes 5/1,438,726 · genomes 1/152,196 · joint denominator

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.Ala604Val
Coding: c.1811C>T
MANE Select: NM_014844
dbSNP: rs1060502180
Type: single nucleotide variant
Location: chr14:102434628 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 604: 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.Ala604= Likely benign ★ same residue
TECPR2 p.Ala604Thr 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

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-ala604val (accessed [today's date]).

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