ECM1 p.Trp362Ter
c.1085G>A · VCV4855518
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
lipoid proteinosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 8 of 10 |
| Splicing | ||
| SpliceAI | Δ0.86 | acceptor gain · deltas |
| Pangolin | Δ0.56 | gain · loss 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 54.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ECM1
- Protein
- p.Trp362Ter
- Coding
- c.1085G>A
- MANE Select
- NM_004425
- Type
- single nucleotide variant
- Location
- chr1:150512353 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.05
- Residue 362
- the '2 x approximate repeats' region
Similar variants
- ECM1 p.Arg254Ter Pathogenic ★★ same condition
- ECM1 p.Arg416Ter Pathogenic/Likely pathogenic ★★ same condition
- ECM1 p.Arg53Ter Pathogenic ★★ same condition
- ECM1 p.Cys269Tyr Pathogenic/Likely pathogenic ★★ same condition
- ECM1 c.122-3T>G Uncertain significance ★★ same condition
- ECM1 p.Pro169Ala Uncertain significance ★★ same condition
- ECM1 p.Ser250Leu Uncertain significance ★★ ⚠ same condition
- ECM1 c.1083+10C>T Benign/Likely benign ★★ 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-trp362ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown