Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 27.8%, sas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.51 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.8 |
| Overall | ||
| CADD | 0.416 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
27.8%
South Asian · 25,296/90,848 alleles
Filtering AF
27.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 27.4%
Overall
14%
225,992/1,608,500 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 27.8% | 4 |
| Middle Eastern | 20.7% | 5 |
| African / African-American | 19.7% | 5 |
| Amishnot grpmax-eligible | 14.8% | 7 |
| Remaining individualsnot grpmax-eligible | 14.1% | 7 |
| European (non-Finnish) | 13.1% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 12.7% | 8 |
| Admixed American | 12.1% | 8 |
| Finnishnot grpmax-eligible | 10.4% | 10 |
| East Asian | 9.57% | 10 |
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
- ECH1
- Protein
- p.Ser125=
- Coding
- c.375G>A
- MANE Select
- NM_001398
- dbSNP
- rs15570
- Type
- single nucleotide variant
- Location
- chr19:38817550 (GRCh38)
- Gene constraint
- LOEUF 1.083 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.61 · 2 PDB
- Residue 125
- an α-helix
Similar variants
- ECH1 p.Lys95Arg Uncertain significance ★★ ⚠ same type
- ECH1 p.Ala226Thr Uncertain significance ★ ⚠ same type
- ECH1 p.Ala237Val Uncertain significance ★ ⚠ same type
- ECH1 p.Ala259Thr Uncertain significance ★ ⚠ same type
- ECH1 p.Ala3Thr Uncertain significance ★ ⚠ same type
- ECH1 p.Ala50Thr Uncertain significance ★ ⚠ same type
- ECH1 p.Arg137Trp Uncertain significance ★ ⚠ same type
- ECH1 p.Arg143His Uncertain significance ★ ⚠ 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/ech1-p-ser125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown