ENPP2 p.Gly388=
c.1164A>G · VCV3341517
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.719%, nfe)
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 0.45 | GERP -0.79, phastCons 1 |
| Overall | ||
| CADD | 8.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.719%
European (non-Finnish) · 8,435/1,173,334 alleles
Filtering AF
0.706%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.701%
Overall
0.595%
9,520/1,599,224 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.719% | 139 |
| Remaining individualsnot grpmax-eligible | 0.572% | 175 |
| Admixed American | 0.562% | 178 |
| Ashkenazi Jewishnot grpmax-eligible | 0.348% | 288 |
| Finnishnot grpmax-eligible | 0.255% | 392 |
| Middle Eastern | 0.234% | 428 |
| African / African-American | 0.148% | 675 |
| South Asian | 0.0204% | 4,895 |
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
- ENPP2
- Protein
- p.Gly388=
- Coding
- c.1164A>G
- MANE Select
- NM_001040092
- Type
- single nucleotide variant
- Location
- chr8:119590548 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 91.61 · 9 PDB
- Residue 388
- a β-strand; a disulfide bond; the 'phosphodiesterase' region
Similar variants
- ENPP2 p.Arg799Trp Uncertain significance ★★ ⚠ same type
- ENPP2 c.973-2122T>C Benign ★★ same type
- ENPP2 c.973-2129G>A Benign ★★ same type
- ENPP2 p.Arg844Cys Benign/Likely benign ★★ same type
- ENPP2 c.1781-1341A>C Uncertain significance ★ same type
- ENPP2 c.973-1995C>A Uncertain significance ★ same type
- ENPP2 c.973-1998C>T Uncertain significance ★ same type
- ENPP2 c.973-2023G>C 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/enpp2-p-gly388 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown