Is ECM1 p.Trp359Ter (c.1077G>A) pathogenic?

ECM1 p.Trp359Ter (c.1077G>A) is classified Pathogenic in ECM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Very rare (popmax 0.00647%, nfe); Associated with lipoid proteinosis.

What condition is associated with ECM1 p.Trp359Ter (c.1077G>A)?

ECM1 p.Trp359Ter (c.1077G>A) is associated with lipoid proteinosis (ClinVar).

How common is ECM1 p.Trp359Ter (c.1077G>A) in the general population?

ECM1 p.Trp359Ter (c.1077G>A) is very rare (popmax 0.00647%, nfe) (gnomAD).

ECM1 p.Trp359Ter

c.1077G>A · VCV4078669

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00647%, nfe)

Conditions

lipoid proteinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 10
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.89 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Overall
CADD	38.0	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 0.00647% European (non-Finnish) · 76/1,174,422 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00484%

Overall 0.00486% 78/1,604,826 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00647%	15,453
Remaining individualsnot grpmax-eligible	0.00161%	62,030
Finnishnot grpmax-eligible	0.00157%	63,552

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.Trp359Ter
Coding: c.1077G>A
MANE Select: NM_004425
Type: single nucleotide variant
Location: chr1:150511825 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 359: the '2 x approximate repeats' 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.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-trp359ter (accessed [today's date]).

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