ECHS1 p.Leu8=
c.22C>T · rs1478946630 · VCV2500448
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00289%, afr)
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 0.62 | phastCons 0.085 |
| Overall | ||
| CADD | 5.289 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00289%
African / African-American · 2/69,232 alleles
Filtering AF
0.000479%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000179%
Overall
0.000266%
4/1,502,744 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00289% | 34,616 |
| European (non-Finnish) | 0.000177% | 565,825 |
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
- Protein
- p.Leu8=
- Coding
- c.22C>T
- MANE Select
- NM_004092
- dbSNP
- rs1478946630
- Type
- single nucleotide variant
- Location
- chr10:133373312 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
Similar variants
- ECHS1 p.Leu8Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
- ECHS1 c.414+1G>A Pathogenic/Likely pathogenic ★★ same type
- ECHS1 c.88+5G>A Pathogenic/Likely pathogenic ★★ same type
- ECHS1 p.Ala132Thr Pathogenic/Likely pathogenic ★★ same type
- ECHS1 p.Ala173Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- ECHS1 p.Ala238Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- ECHS1 p.Ala278Thr Likely pathogenic ★★ same type
- ECHS1 p.Ala2Val 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/echs1-p-leu8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown