Is ENTPD1 p.Glu173= (c.519G>A) pathogenic?

ENTPD1 p.Glu173= (c.519G>A) is classified Likely benign in ENTPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 64.

What condition is associated with ENTPD1 p.Glu173= (c.519G>A)?

ENTPD1 p.Glu173= (c.519G>A) is associated with hereditary spastic paraplegia 64 (ClinVar).

How common is ENTPD1 p.Glu173= (c.519G>A) in the general population?

ENTPD1 p.Glu173= (c.519G>A) is absent from gnomAD v4.1 (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.Glu173=

c.519G>A · VCV3715948

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 64

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.89	GERP -3.4, phastCons 1
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ENTPD1
Protein: p.Glu173=
Coding: c.519G>A
MANE Select: NM_001776
Type: single nucleotide variant
Location: chr10:95844581 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.85

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

Similar variants

ENTPD1 p.Leu370Ter Pathogenic ★★ same condition
ENTPD1 p.Tyr287Ter Pathogenic ★★ same condition
ENTPD1 p.Arg147Ser Uncertain significance ★★ ⚠ same condition
ENTPD1 p.Glu140Ala Uncertain significance ★★ ⚠ same condition
ENTPD1 p.Glu142Gln Uncertain significance ★★ ⚠ same condition
ENTPD1 p.Glu231Lys Uncertain significance ★★ ⚠ same condition
ENTPD1 p.Glu380Gly Uncertain significance ★★ ⚠ same condition
ENTPD1 p.Glu395Asp Uncertain significance ★★ ⚠ 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/entpd1-p-glu173 (accessed [today's date]).

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