Is ENTPD1 p.Tyr63= (c.189C>T) pathogenic?

ENTPD1 p.Tyr63= (c.189C>T) is classified Likely benign in ENTPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Very rare (popmax 0.00329%, sas); Associated with hereditary spastic paraplegia 64.

What condition is associated with ENTPD1 p.Tyr63= (c.189C>T)?

ENTPD1 p.Tyr63= (c.189C>T) is associated with hereditary spastic paraplegia 64 (ClinVar).

How common is ENTPD1 p.Tyr63= (c.189C>T) in the general population?

ENTPD1 p.Tyr63= (c.189C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Autosomal recessive spastic paraplegia type 64 inherited?

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

ENTPD1 p.Tyr63=

c.189C>T · rs2494329534 · VCV2180493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

hereditary spastic paraplegia 64

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 1.4	GERP -0.82, phastCons 1
Overall
CADD	8.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,076 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,876 alleles · very rare

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: ENTPD1
Protein: p.Tyr63=
Coding: c.189C>T
dbSNP: rs2494329534
Type: single nucleotide variant
Location: chr10:95839735 (GRCh38)

Full ENTPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 64 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 64 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, 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/entpd1-p-tyr63 (accessed [today's date]).

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