ECHS1 p.Ala222=
c.666C>T · rs775160487 · VCV384258
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 1.8 | phastCons 1 |
| Overall | ||
| CADD | 9.157 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,000 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000248%
4/1,613,782 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,000 |
| African / African-American | 0.00267% | 37,459 |
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.Ala222=
- Coding
- c.666C>T
- MANE Select
- NM_004092
- dbSNP
- rs775160487
- Type
- single nucleotide variant
- Location
- chr10:133366049 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
- Residue 222
- an α-helix
Similar variants
- ECHS1 p.Ala222Thr Likely pathogenic ★ ⚠ 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-ala222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown