Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11.9%, afr) — 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.6 | |
| Overall | ||
| CADD | 1.632 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.9%
African / African-American · 8,909/75,026 alleles
Filtering AF
11.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.6%
Overall
0.663%
10,692/1,612,144 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.9% | 8 |
| Remaining individualsnot grpmax-eligible | 0.929% | 108 |
| Admixed American | 0.836% | 120 |
| Middle Eastern | 0.528% | 189 |
| East Asian | 0.506% | 198 |
| Ashkenazi Jewishnot grpmax-eligible | 0.193% | 519 |
| South Asian | 0.0803% | 1,245 |
| European (non-Finnish) | 0.0266% | 3,757 |
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.Phe76=
- Coding
- c.228C>T
- MANE Select
- NM_004092
- dbSNP
- rs2230260
- Type
- single nucleotide variant
- Location
- chr10:133370618 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 6 PDB
- Residue 76
- an α-helix
Similar variants
- ECHS1 p.Phe76Cys Uncertain significance ★ 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-phe76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown