ECHS1 p.Ala2=
c.6C>T · rs375706106 · VCV1533721
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00613%, sas)
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 -5.4 | |
| Overall | ||
| CADD | 1.156 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00613%
South Asian · 5/81,600 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0015%
Overall
0.000599%
9/1,502,884 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00613% | 16,320 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00367% | 27,216 |
| Remaining individualsnot grpmax-eligible | 0.00171% | 58,432 |
| European (non-Finnish) | 0.000177% | 566,033 |
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.Ala2=
- Coding
- c.6C>T
- MANE Select
- NM_004092
- dbSNP
- rs375706106
- Type
- single nucleotide variant
- Location
- chr10:133373328 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
- Residue 2
- a UniProt-annotated variant site (in echs1d)
Similar variants
- ECHS1 p.Ala2Val Pathogenic ★★ ⚠ same residue
- ECHS1 p.Ala2Ser Uncertain significance ★ ⚠ same residue
- ECHS1 p.Ala2fs 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
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-ala2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown