ECM1 p.Ile414=
c.1242C>T · rs200585596 · VCV709803
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0626%, nfe)
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 0.87 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 12.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0626%
European (non-Finnish) · 739/1,179,994 alleles
Filtering AF
0.0589%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0574%
Overall
0.0504%
813/1,613,898 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0626% | 1,597 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0574% | 1,741 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Finnishnot grpmax-eligible | 0.0281% | 3,556 |
| African / African-American | 0.0173% | 5,765 |
| Admixed American | 0.00334% | 29,974 |
| East Asian | 0.00223% | 44,860 |
| South Asian | 0.0011% | 91,068 |
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
- ECM1
- Protein
- p.Ile414=
- Coding
- c.1242C>T
- MANE Select
- NM_004425
- dbSNP
- rs200585596
- Type
- single nucleotide variant
- Location
- chr1:150512510 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.05
Similar variants
- ECM1 p.Arg254Ter Pathogenic ★★ same type
- ECM1 p.Arg416Ter Pathogenic/Likely pathogenic ★★ same type
- ECM1 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same type
- ECM1 p.Arg53Ter Pathogenic ★★ same type
- ECM1 p.Cys269Tyr Pathogenic/Likely pathogenic ★★ same type
- ECM1 c.122-3T>G Uncertain significance ★★ same type
- ECM1 p.Arg185His Uncertain significance ★★ ⚠ same type
- ECM1 p.Asn324His 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/ecm1-p-ile414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown