Is ECM1 p.Ala484fs (c.1450_1454del) pathogenic?

ECM1 p.Ala484fs (c.14501454del) is classified Pathogenic in ECM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-07). Very rare (popmax 0.000424%, nfe); Associated with lipoid proteinosis.

What condition is associated with ECM1 p.Ala484fs (c.1450_1454del)?

ECM1 p.Ala484fs (c.1450_1454del) is associated with lipoid proteinosis (ClinVar).

How common is ECM1 p.Ala484fs (c.1450_1454del) in the general population?

ECM1 p.Ala484fs (c.1450_1454del) is very rare (popmax 0.000424%, nfe) (gnomAD).

ECM1 p.Ala484fs

c.1450_1454del · rs867426247 · VCV1802155

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 2.3, phastCons 1
Overall
CADD	32.0	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,022 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,984 alleles · very 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.Ala484fs
Coding: c.1450_1454del
MANE Select: NM_004425
dbSNP: rs867426247
Type: Deletion
Location: chr1:150513290 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05

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.Arg171fs Pathogenic ★ same condition
ECM1 p.Arg430fs Pathogenic ★ same condition
ECM1 p.Gln340fs Likely pathogenic ★ same condition
ECM1 p.Ser48fs Likely pathogenic ★ same condition
ECM1 c.1304+35_*302del 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-ala484fs (accessed [today's date]).

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