ENPP1 p.Pro40=
c.120C>T · rs553929139 · VCV744088
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0694%, afr)
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 -0.95 | GERP -1.8 |
| Overall | ||
| CADD | 8.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0694%
African / African-American · 47/67,686 alleles
Filtering AF
0.0536%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.048%
Overall
0.00407%
59/1,448,786 alleles · ultra-rare
exomes 27/1,297,844 · genomes 32/150,942 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0694% | 1,440 |
| Remaining individualsnot grpmax-eligible | 0.00546% | 18,325 |
| Admixed American | 0.00499% | 20,053 |
| European (non-Finnish) | 0.000639% | 156,442 |
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
- ENPP1
- Protein
- p.Pro40=
- Coding
- c.120C>T
- MANE Select
- NM_006208
- dbSNP
- rs553929139
- Type
- single nucleotide variant
- Location
- chr6:131808155 (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 40
- the 'disordered' region
Similar variants
- ENPP1 p.Pro40Thr Likely benign ★★ 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
- ENPP1 p.Arg476Ter Pathogenic ★★ same type
- ENPP1 p.Arg481Trp 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-pro40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown