ECM1 p.Leu504=
c.1512G>A · rs146676314 · VCV799395
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00237%, nfe)
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 Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 0.31, phastCons 1 |
| Overall | ||
| CADD | 7.749 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00237%
European (non-Finnish) · 28/1,180,044 alleles
Filtering AF
0.00164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00142%
Overall
0.00186%
30/1,614,096 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00237% | 42,144 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00133% | 74,938 |
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.Leu504=
- Coding
- c.1512G>A
- MANE Select
- NM_004425
- dbSNP
- rs146676314
- Type
- single nucleotide variant
- Location
- chr1:150513356 (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-leu504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown