ECM1 p.Pro77=
c.231C>T · rs115614690 · VCV772686
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.65%, afr)
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 · C>G here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.034 | GERP -1.4 |
| Overall | ||
| CADD | 5.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.65%
African / African-American · 1,985/75,010 alleles
Filtering AF
2.55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.51%
Overall
0.135%
2,183/1,614,084 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.65% | 38 |
| Remaining individualsnot grpmax-eligible | 0.162% | 619 |
| Admixed American | 0.113% | 883 |
| Middle Eastern | 0.066% | 1,516 |
| South Asian | 0.0132% | 7,590 |
| European (non-Finnish) | 0.0011% | 90,768 |
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.Pro77=
- Coding
- c.231C>T
- MANE Select
- NM_004425
- dbSNP
- rs115614690
- Type
- single nucleotide variant
- Location
- chr1:150509929 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.05
- Residue 77
- the 'disordered' region
Similar variants
- ECM1 p.Pro77Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro77 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown