ECE1 p.Ala243=
c.729C>T · rs763305486 · VCV735770
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
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 · G>T here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.4 | GERP -3.8 |
| Overall | ||
| CADD | 5.303 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/91,084 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.00452%
73/1,614,034 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,506 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| European (non-Finnish) | 0.00432% | 23,138 |
| East Asian | 0.00223% | 44,896 |
| Admixed American | 0.00167% | 60,000 |
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.Ala243=
- Coding
- c.729C>T
- MANE Select
- NM_001397
- dbSNP
- rs763305486
- Type
- single nucleotide variant
- Location
- chr1:21258726 (GRCh38)
- Gene constraint
- LOEUF 0.482 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 91.16 · 1 PDB
- Residue 243
- a disulfide bond; the peptidase m13 domain; a β-strand
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.Asp547= 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-ala243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown