Is ENTPD1 p.Val293Ile (c.877G>A) pathogenic?

ENTPD1 p.Val293Ile (c.877G>A) is classified Benign in ENTPD1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0753); Common (popmax 5.72%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spastic paraplegia 64.

What condition is associated with ENTPD1 p.Val293Ile (c.877G>A)?

ENTPD1 p.Val293Ile (c.877G>A) is associated with hereditary spastic paraplegia 64, hereditary spastic paraplegia (ClinVar).

How is Autosomal recessive spastic paraplegia type 64 inherited?

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

What do computational predictors say about ENTPD1 p.Val293Ile (c.877G>A)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

ENTPD1 p.Val293Ile

Q: How common is ENTPD1 p.Val293Ile (c.877G>A) in the general population?

ENTPD1 p.Val293Ile (c.877G>A) is common (popmax 5.72%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.877G>A · rs3793744 · VCV703843

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.72%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 64

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.8	GERP -3.6
Regional constraint	o/e 0.83	unconstrained · MANE · 110 kb · p 3.1e-05 · regional, not allelic
Overall
CADD	0.029	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.72% African / African-American · 4,288/75,014 alleles

Filtering AF 5.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.52%

Overall 0.343% 5,532/1,614,134 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.72%	17
East Asian	1.16%	86
Remaining individualsnot grpmax-eligible	0.509%	197
Admixed American	0.376%	266
Middle Eastern	0.33%	303
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
South Asian	0.0198%	5,060
European (non-Finnish)	0.0108%	9,292

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.Val293Ile
Coding: c.877G>A
dbSNP: rs3793744
Type: single nucleotide variant
Location: chr10:95847509 (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

Also linked: hereditary spastic paraplegia

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-val293ile (accessed [today's date]).

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