Is NT5C2 p.Thr489= (c.1467G>A) pathogenic?

NT5C2 p.Thr489= (c.1467G>A) is classified Likely benign in NT5C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). Very rare (popmax 0.00447%, eas); Associated with hereditary spastic paraplegia 45.

What condition is associated with NT5C2 p.Thr489= (c.1467G>A)?

NT5C2 p.Thr489= (c.1467G>A) is associated with hereditary spastic paraplegia 45 (ClinVar).

How common is NT5C2 p.Thr489= (c.1467G>A) in the general population?

NT5C2 p.Thr489= (c.1467G>A) is very rare (popmax 0.00447%, eas) (gnomAD).

How is Autosomal recessive spastic paraplegia type 45 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NT5C2 p.Thr489=

c.1467G>A · rs368637290 · VCV658793

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

hereditary spastic paraplegia 45

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.5	GERP -5
Overall
CADD	2.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,720 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00193% 31/1,604,808 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,360
African / African-American	0.00269%	37,230
European (non-Finnish)	0.00204%	48,963
Admixed American	0.0017%	58,722
Remaining individualsnot grpmax-eligible	0.00161%	62,080
South Asian	0.00111%	89,804

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: NT5C2
Protein: p.Thr489=
Coding: c.1467G>A
MANE Select: NM_017649 · reported on NM_001351169
dbSNP: rs368637290
Type: single nucleotide variant
Location: chr10:103089891 (GRCh38)

Full NT5C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 45 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

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/nt5c2-p-thr489 (accessed [today's date]).

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