Is ENTPD1 p.Tyr418= (c.1254C>T) pathogenic?

ENTPD1 p.Tyr418= (c.1254C>T) is classified Likely benign in ENTPD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-06). Ultra-rare (popmax 0.0165%, mid); Associated with hereditary spastic paraplegia 64.

What condition is associated with ENTPD1 p.Tyr418= (c.1254C>T)?

ENTPD1 p.Tyr418= (c.1254C>T) is associated with hereditary spastic paraplegia 64 (ClinVar).

How common is ENTPD1 p.Tyr418= (c.1254C>T) in the general population?

ENTPD1 p.Tyr418= (c.1254C>T) is ultra-rare (popmax 0.0165%, mid) (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.Tyr418=

c.1254C>T · rs759450413 · VCV706081

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 0.4	GERP -0.23, phastCons 0.99
Overall
CADD	8.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00229% 37/1,613,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.008%	12,498
African / African-American	0.004%	24,973
European (non-Finnish)	0.00229%	43,703
Admixed American	0.00167%	59,992

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.Tyr418=
Coding: c.1254C>T
dbSNP: rs759450413
Type: single nucleotide variant
Location: chr10:95864789 (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-tyr418 (accessed [today's date]).

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