Is ENTPD1 p.Val9Met (c.25G>A) pathogenic?

ENTPD1 p.Val9Met (c.25G>A) is classified Conflicting classifications of pathogenicity in ENTPD1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.0982); Rare (popmax 0.125%, nfe); Associated with hereditary spastic paraplegia 64.

What condition is associated with ENTPD1 p.Val9Met (c.25G>A)?

ENTPD1 p.Val9Met (c.25G>A) is associated with hereditary spastic paraplegia 64, polymicrogyria, microcephaly (ClinVar).

How common is ENTPD1 p.Val9Met (c.25G>A) in the general population?

ENTPD1 p.Val9Met (c.25G>A) is rare (popmax 0.125%, nfe) (gnomAD).

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.Val9Met (c.25G>A)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

ENTPD1 p.Val9Met

c.25G>A · rs150772804 · VCV374088

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 64

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP -2.6, phastCons 0.62
Regional constraint	o/e 0.83	unconstrained · MANE · 110 kb · p 3.1e-05 · regional, not allelic
Overall
CADD	15.94	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 0.125% European (non-Finnish) · 1,475/1,179,944 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.0961% 1,551/1,614,030 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.125%	800
Remaining individualsnot grpmax-eligible	0.0688%	1,454
Admixed American	0.0283%	3,531
African / African-American	0.0187%	5,361
South Asian	0.0022%	45,540

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.Val9Met
Coding: c.25G>A
dbSNP: rs150772804
Type: single nucleotide variant
Location: chr10:95823245 (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: polymicrogyria microcephaly 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-val9met (accessed [today's date]).

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