Is ENTPD3 p.Leu37Phe (c.109C>T) pathogenic?

ENTPD3 p.Leu37Phe (c.109C>T) is classified Uncertain significance in ENTPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely benign (0.1763); Absent from gnomAD v4.1.

How common is ENTPD3 p.Leu37Phe (c.109C>T) in the general population?

ENTPD3 p.Leu37Phe (c.109C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENTPD3 p.Leu37Phe (c.109C>T)?

AlphaMissense predicts likely benign (score 0.1763) — an in-silico prediction, not a clinical call.

ENTPD3 p.Leu37Phe

c.109C>T · VCV3275536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1763	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP 1.8, phastCons 0.069
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.058 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

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: ENTPD3
Protein: p.Leu37Phe
Coding: c.109C>T
MANE Select: NM_001248
Type: single nucleotide variant
Location: chr3:40392091 (GRCh38)
Gene constraint: LOEUF 1.454 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.79

Full ENTPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD3 p.Ala140Val Uncertain significance ★ ⚠ same type
ENTPD3 p.Ala17Ser Uncertain significance ★ ⚠ same type
ENTPD3 p.Ala223Val Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg143His Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg292Gln Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg292Trp Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg419Cys Uncertain significance ★ ⚠ same type
ENTPD3 p.Arg419His Uncertain significance ★ ⚠ same type

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/entpd3-p-leu37phe (accessed [today's date]).

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