Is ENTPD2 p.Lys4Glu (c.10A>G) pathogenic?

ENTPD2 p.Lys4Glu (c.10A>G) is classified Uncertain significance in ENTPD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: likely benign (0.1003); Ultra-rare (popmax 0.0265%, eas).

How common is ENTPD2 p.Lys4Glu (c.10A>G) in the general population?

ENTPD2 p.Lys4Glu (c.10A>G) is ultra-rare (popmax 0.0265%, eas) (gnomAD).

What do computational predictors say about ENTPD2 p.Lys4Glu (c.10A>G)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

ENTPD2 p.Lys4Glu

c.10A>G · rs539623884 · VCV3089059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0265%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,337 bp · p 0.028 · regional, not allelic
Overall
CADD	26.0	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 0.0265% East Asian · 8/30,188 alleles

Filtering AF 0.0131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00958%

Overall 0.00116% 14/1,202,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0265%	3,773
South Asian	0.0124%	8,056
Remaining individualsnot grpmax-eligible	0.00452%	22,115
European (non-Finnish)	0.000104%	966,184

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: ENTPD2
Protein: p.Lys4Glu
Coding: c.10A>G
MANE Select: NM_203468
dbSNP: rs539623884
Type: single nucleotide variant
Location: chr9:137053988 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.02

Full ENTPD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD2 p.Arg193Gln Benign ★★ same type
ENTPD2 p.Val343= Benign ★★ same type
ENTPD2 p.Ala113Thr Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala113Val Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala16Gly Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala17Thr Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala199Ser Uncertain significance ★ ⚠ same type
ENTPD2 p.Ala20Ser 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/entpd2-p-lys4glu (accessed [today's date]).

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