Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 38.5%, 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 2.6 | GERP 0.6, phastCons 1 |
| Overall | ||
| CADD | 8.422 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
38.5%
African / African-American · 28,864/74,916 alleles
Filtering AF
38.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 38%
Overall
5.45%
87,985/1,613,554 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 38.5% | 3 |
| Middle Eastern | 6.69% | 15 |
| Remaining individualsnot grpmax-eligible | 6.39% | 16 |
| Finnishnot grpmax-eligible | 6.31% | 16 |
| Admixed American | 4.73% | 21 |
| Ashkenazi Jewishnot grpmax-eligible | 4.11% | 24 |
| European (non-Finnish) | 3.76% | 27 |
| Amishnot grpmax-eligible | 3.08% | 33 |
| South Asian | 2.36% | 42 |
| East Asian | 0.198% | 504 |
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
- ECE1
- Protein
- p.Asp547=
- Coding
- c.1641T>C
- MANE Select
- NM_001397
- dbSNP
- rs2228321
- Type
- single nucleotide variant
- Location
- chr1:21233587 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 91.16 · 1 PDB
- Residue 547
- a disulfide bond; the peptidase m13 domain; a turn
Similar variants
- ECE1 p.Thr312Met Uncertain significance ★★ ⚠ same type
- ECE1 c.1020+15G>A Benign ★★ same type
- ECE1 c.1164-5C>T Benign ★★ same type
- ECE1 c.1278+7C>T Benign ★★ same type
- ECE1 c.1782-4C>A Benign ★★ same type
- ECE1 c.828+8T>C Benign ★★ same type
- ECE1 p.Asn397Ser Benign ★★ same type
- ECE1 p.Glu173Lys Likely benign ★★ 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/ece1-p-asp547 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown