Is ENTPD7 p.Pro347Ser (c.1039C>T) pathogenic?

ENTPD7 p.Pro347Ser (c.1039C>T) is classified Uncertain significance in ENTPD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.084); Ultra-rare (popmax 0.0187%, sas).

How common is ENTPD7 p.Pro347Ser (c.1039C>T) in the general population?

ENTPD7 p.Pro347Ser (c.1039C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

What do computational predictors say about ENTPD7 p.Pro347Ser (c.1039C>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

ENTPD7 p.Pro347Ser

c.1039C>T · VCV4249333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 41 kb · p 0.0028 · regional, not allelic
Overall
CADD	17.91	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 0.0187% South Asian · 17/91,056 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.0015% 22/1,461,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,356
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	8.47e-05%	1,179,988

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: ENTPD7
Protein: p.Pro347Ser
Coding: c.1039C>T
MANE Select: NM_078470 · reported on NM_020354
Type: single nucleotide variant
Location: chr10:99698562 (GRCh38)

Full ENTPD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/entpd7-p-pro347ser (accessed [today's date]).

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