ECHS1 p.Gly140=
c.420C>T · rs751113264 · VCV511826
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.8 | |
| Overall | ||
| CADD | 0.856 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
East Asian · 10/44,884 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00916%
Overall
0.00155%
25/1,613,262 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0223% | 4,488 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,454 |
| African / African-American | 0.00133% | 74,914 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.00102% | 98,322 |
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.Gly140=
- Coding
- c.420C>T
- MANE Select
- NM_004092
- dbSNP
- rs751113264
- Type
- single nucleotide variant
- Location
- chr10:133369017 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
Similar variants
- 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
- ECHS1 p.Arg54Cys 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-gly140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown