ECHS1 p.Ala3=
c.9C>A · rs370494262 · VCV1899094
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0101%, 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 -1.1 | |
| Overall | ||
| CADD | 3.793 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0101%
African / African-American · 7/69,298 alleles
Filtering AF
0.00469%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00329%
Overall
0.000665%
10/1,502,910 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0101% | 9,900 |
| Remaining individualsnot grpmax-eligible | 0.00342% | 29,232 |
| European (non-Finnish) | 8.83e-05% | 1,131,976 |
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.Ala3=
- Coding
- c.9C>A
- MANE Select
- NM_004092
- dbSNP
- rs370494262
- Type
- single nucleotide variant
- Location
- chr10:133373325 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
Similar variants
- ECHS1 p.Ala3Asp Likely pathogenic ★ ⚠ same residue
- ECHS1 p.Ala3Pro Likely pathogenic ★ ⚠ same residue
- ECHS1 p.Ala3Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- ECHS1 p.Ala3Val 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
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-ala3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown