ECHS1 c.286+4C>A
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00113%, nfe)
Conditions
1
ECHS1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.56 | |
| Overall | ||
| CADD | 0.058 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00113%
European (non-Finnish) · 13/1,150,448 alleles
Filtering AF
0.000631%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000486%
Overall
0.000835%
13/1,556,602 alleles · very rare
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
- ECHS1
- Coding
- c.286+4C>A
- MANE Select
- NM_004092
- dbSNP
- rs181328051
- Type
- single nucleotide variant
- Location
- chr10:133370556 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
Disease context
ECHS1-related disorder
Similar variants
- ECHS1 p.Arg54Cys Pathogenic/Likely pathogenic ★★ same condition
- ECHS1 p.Asn59Ser Pathogenic/Likely pathogenic ★★ same condition
- ECHS1 p.Thr180Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ECHS1 p.Thr277Ile Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ECHS1 c.89-2A>G Likely pathogenic ★ same condition
- ECHS1 p.Gly175Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
- ECHS1 p.Tyr153Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
- ECHS1 p.Leu193= Likely benign same condition
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/echs1-c-286-plus-4c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown