Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.97%, amr) — too common for a highly-penetrant pathogenic allele
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 -4 | GERP -3.5 |
| Overall | ||
| CADD | 3.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.97%
Admixed American · 4,183/60,028 alleles
Filtering AF
6.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.72%
Overall
0.274%
4,421/1,614,196 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 6.97% | 14 |
| Remaining individualsnot grpmax-eligible | 0.2% | 500 |
| African / African-American | 0.0866% | 1,154 |
| East Asian | 0.00668% | 14,962 |
| South Asian | 0.00659% | 15,180 |
| European (non-Finnish) | 0.00322% | 31,054 |
| Finnishnot grpmax-eligible | 0.00156% | 64,038 |
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
- ENPP6
- Protein
- p.Ser71=
- Coding
- c.213G>A
- MANE Select
- NM_153343
- dbSNP
- rs4861612
- Type
- single nucleotide variant
- Location
- chr4:184217607 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.06
- Residue 71
- a modified residue (phosphoserine); an active site; a binding site
Similar variants
- ENPP6 p.Ser71Leu Uncertain significance ★ ⚠ same residue
- ENPP6 p.Ala20Asp Uncertain significance ★ ⚠ same type
- ENPP6 p.Ala20Thr Uncertain significance ★ ⚠ same type
- ENPP6 p.Ala212Thr Uncertain significance ★ ⚠ same type
- ENPP6 p.Ala303Pro Uncertain significance ★ ⚠ same type
- ENPP6 p.Ala369Gly Uncertain significance ★ ⚠ same type
- ENPP6 p.Ala380Pro Uncertain significance ★ ⚠ same type
- ENPP6 p.Arg181Pro 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/enpp6-p-ser71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown