Is ECM1 p.Ser48fs (c.142del) pathogenic?

ECM1 p.Ser48fs (c.142del) is classified Likely pathogenic in ECM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-22). No allele count reported in gnomAD v4.1 (AN 1,613,244); Associated with lipoid proteinosis.

What condition is associated with ECM1 p.Ser48fs (c.142del)?

ECM1 p.Ser48fs (c.142del) is associated with lipoid proteinosis (ClinVar).

How common is ECM1 p.Ser48fs (c.142del) in the general population?

ECM1 p.Ser48fs (c.142del) is no allele count reported in gnomAD v4.1 (AN 1,613,244) (gnomAD).

ECM1 p.Ser48fs

c.142del · rs1670380730 · VCV930258

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,244)

Conditions

lipoid proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.8	GERP -2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,244). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ECM1
Protein: p.Ser48fs
Coding: c.142del
MANE Select: NM_004425
dbSNP: rs1670380730
Type: Deletion
Location: chr1:150509681 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 48: the 'disordered' region

Full ECM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lipoid proteinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ECM1 p.Pro78fs Pathogenic/Likely pathogenic ★★ same condition
ECM1 c.1304+33_*300del Pathogenic ★ same condition
ECM1 p.Ala17fs Likely pathogenic ★ same condition
ECM1 p.Ala484fs Pathogenic ★ same condition
ECM1 p.Arg171fs Pathogenic ★ same condition
ECM1 p.Arg430fs Pathogenic ★ same condition
ECM1 p.Gln340fs Likely pathogenic ★ same condition
ECM1 p.Ser48= Likely benign ★ same residue

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-ser48fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown