Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 44.3%, afr) — 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 -0.53 | GERP -0.19, phastCons 0.002 |
| Non-coding constraint | Z 1.55 | 1 kb window · o/e 0.90 · regional · uncalibrated |
| Overall | ||
| CADD | 0.796 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
44.3%
African / African-American · 20,079/45,336 alleles
Filtering AF
43.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 43.6%
Overall
17.7%
41,729/236,352 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 44.3% | 2 |
| Amishnot grpmax-eligible | 19% | 5 |
| Remaining individualsnot grpmax-eligible | 15.3% | 7 |
| Admixed American | 13% | 8 |
| European (non-Finnish) | 12.2% | 8 |
| Finnishnot grpmax-eligible | 9.72% | 10 |
| South Asian | 8.99% | 11 |
| Middle Eastern | 8.73% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 7.96% | 13 |
| East Asian | 4.66% | 21 |
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
- ELN
- Coding
- c.*659G>C
- MANE Select
- NM_000501
- dbSNP
- rs8326
- Type
- single nucleotide variant
- Location
- chr7:74069359 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.20
Similar variants
- ELN c.134-1G>A Likely pathogenic ★★ same type
- ELN c.377-2A>G Pathogenic/Likely pathogenic ★★ same type
- ELN c.643+1G>A Pathogenic/Likely pathogenic ★★ same type
- ELN c.643+1G>C Likely pathogenic ★★ same type
- ELN c.686-2A>G Likely pathogenic ★★ same type
- ELN c.800-1G>A Pathogenic/Likely pathogenic ★★ same type
- ELN c.800-2A>G Pathogenic ★★ same type
- ELN c.800-3C>G 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/eln-c-star-659g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown