ENPP1 p.Pro496=
c.1488T>G · VCV4727755
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 -2.8 | GERP -3 |
| Overall | ||
| CADD | 6.536 | 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.Pro496=
- Coding
- c.1488T>G
- MANE Select
- NM_006208
- Type
- single nucleotide variant
- Location
- chr6:131872973 (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 496
- the 'phosphodiesterase' region
Similar variants
- 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
- ENPP1 p.Arg476Ter Pathogenic ★★ same type
- ENPP1 p.Arg481Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- ENPP1 p.Arg782Ter 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-pro496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown