Is ENPP1 p.Glu2= (c.6G>A) pathogenic?

ENPP1 p.Glu2= (c.6G>A) is classified Likely benign in ENPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-03). Absent from gnomAD v4.1.

How common is ENPP1 p.Glu2= (c.6G>A) in the general population?

ENPP1 p.Glu2= (c.6G>A) is absent from gnomAD v4.1 (gnomAD).

ENPP1 p.Glu2=

c.6G>A · rs2483384973 · VCV2761125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.77, phastCons 1
Overall
CADD	12.33	PHRED · no single calibrated threshold — expert panels disagree

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: ENPP1
Protein: p.Glu2=
Coding: c.6G>A
MANE Select: NM_006208
dbSNP: rs2483384973
Type: single nucleotide variant
Location: chr6:131808041 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.35 · 7 PDB
Residue 2: the 'disordered' region

Full ENPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENPP1 p.Glu2Ter Pathogenic ★ same residue
ENPP1 p.Glu2Gly Uncertain significance ★ ⚠ same residue
ENPP1 p.Glu2fs Likely pathogenic ★ same residue
ENPP1 c.2230+1G>A Pathogenic ★★ same type
ENPP1 c.2608-1G>A Likely pathogenic ★★ same type
ENPP1 c.313+1G>A Pathogenic/Likely pathogenic ★★ same type
ENPP1 c.715+1G>C Pathogenic/Likely pathogenic ★★ same type
ENPP1 p.Arg456Ter Pathogenic/Likely pathogenic ★★ 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/enpp1-p-glu2 (accessed [today's date]).

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