Is ENTPD3 p.Pro366Arg (c.1097C>G) pathogenic?

ENTPD3 p.Pro366Arg (c.1097C>G) is classified Uncertain significance in ENTPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely benign (0.0749); Very rare (popmax 0.0067%, afr).

How common is ENTPD3 p.Pro366Arg (c.1097C>G) in the general population?

ENTPD3 p.Pro366Arg (c.1097C>G) is very rare (popmax 0.0067%, afr) (gnomAD).

What do computational predictors say about ENTPD3 p.Pro366Arg (c.1097C>G)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

ENTPD3 p.Pro366Arg

c.1097C>G · VCV3845035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -3.29	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 1.7	GERP -0.83, phastCons 0.002
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.058 · regional, not allelic
Overall
CADD	19.64	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

Grpmax group 0.0067% African / African-American · 5/74,674 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000373% 6/1,610,308 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0067%	14,935
European (non-Finnish)	8.49e-05%	1,177,682

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: ENTPD3
Protein: p.Pro366Arg
Coding: c.1097C>G
MANE Select: NM_001248
Type: single nucleotide variant
Location: chr3:40423115 (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-pro366arg (accessed [today's date]).

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