ENPP1 p.Phe113=
c.339C>T · VCV4893993
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00407%, 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 -0.28 | GERP -1.1, phastCons 0.42 |
| Overall | ||
| CADD | 13.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00407%
European (non-Finnish) · 48/1,179,808 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00316%
51/1,613,722 alleles · very rare
exomes 49/1,461,612 · genomes 2/152,110 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00407% | 24,579 |
| South Asian | 0.0022% | 45,540 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
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.Phe113=
- Coding
- c.339C>T
- MANE Select
- NM_006208
- Type
- single nucleotide variant
- Location
- chr6:131850015 (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 113
- the smb 1 domain
Similar variants
- ENPP1 p.Phe113Leu Uncertain significance ★ ⚠ 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-phe113 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown