Is ECM1 p.Ser293= (c.879G>A) pathogenic?

ECM1 p.Ser293= (c.879G>A) is classified Likely pathogenic in ECM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). Very rare (popmax 0.00668%, eas); Associated with ECM1-related disorders.

What condition is associated with ECM1 p.Ser293= (c.879G>A)?

ECM1 p.Ser293= (c.879G>A) is associated with ECM1-related disorders (ClinVar).

How common is ECM1 p.Ser293= (c.879G>A) in the general population?

ECM1 p.Ser293= (c.879G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

ECM1 p.Ser293=

c.879G>A · VCV4909938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

ECM1-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.95	acceptor gain · deltas
Pangolin	Δ0.71	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.035	GERP -0.43
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,882 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00322% 52/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
European (non-Finnish)	0.0039%	25,653
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ser293=
Coding: c.879G>A
MANE Select: NM_004425
Type: single nucleotide variant
Location: chr1:150511627 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 293: the '2 x approximate repeats' region

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

Disease context

ECM1-related disorders

Similar variants

ECM1 p.Ser293Leu Uncertain significance ★ ⚠ same residue
ECM1 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same condition
ECM1 p.Val10Gly Pathogenic ★ same condition
ECM1 p.Phe167Val Uncertain significance ★ ⚠ same condition
ECM1 p.Cys269= Likely benign same condition
ECM1 p.Pro49Gln Likely benign same condition
ECM1 p.Tyr43= Likely benign same condition
ECM1 p.Arg171fs 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-ser293 (accessed [today's date]).

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