ECM1 p.Cys269=
c.807C>T · rs374599359 · VCV3053380
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, afr)
Conditions
1
ECM1-related disorder
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 4.9 | GERP 0.78, phastCons 1 |
| Overall | ||
| CADD | 16.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
African / African-American · 13/74,936 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00813%
Overall
0.000805%
13/1,614,074 alleles · ultra-rare
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.Cys269=
- Coding
- c.807C>T
- MANE Select
- NM_004425
- dbSNP
- rs374599359
- Type
- single nucleotide variant
- Location
- chr1:150511555 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.05
- Residue 269
- the '2 x approximate repeats' region
Disease context
ECM1-related disorder
Similar variants
- ECM1 p.Cys269Tyr Pathogenic/Likely pathogenic ★★ same residue
- ECM1 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same condition
- ECM1 p.Ser293= Likely pathogenic ★ same condition
- ECM1 p.Val10Gly Pathogenic ★ same condition
- ECM1 p.Phe167Val Uncertain significance ★ ⚠ same condition
- ECM1 p.Pro49Gln Likely benign same condition
- ECM1 p.Tyr43= Likely benign same condition
- ECM1 p.Arg171fs Pathogenic ★ same condition
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-cys269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown