ENPP6 c.421+9G>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.731%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +9 | near-intronic (+9 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -2.3 |
| Non-coding constraint | Z 1.10 | 1 kb window · o/e 0.92 · regional · uncalibrated |
| Overall | ||
| CADD | 1.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.731%
African / African-American · 546/74,678 alleles
Filtering AF
0.68%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.66%
Overall
0.0398%
639/1,606,286 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.731% | 137 |
| Admixed American | 0.0684% | 1,463 |
| Remaining individualsnot grpmax-eligible | 0.0531% | 1,884 |
| European (non-Finnish) | 0.0017% | 58,829 |
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
- Coding
- c.421+9G>A
- MANE Select
- NM_153343
- dbSNP
- rs368655804
- Type
- single nucleotide variant
- Location
- chr4:184153545 (GRCh38)
- Gene constraint
- LOEUF 0.997 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.06
Similar variants
- ENPP6 p.Ser71= Benign ★★ same type
- 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-c-421-plus-9g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown