Is ECM1 p.Tyr43= (c.129C>T) pathogenic?

ECM1 p.Tyr43= (c.129C>T) is classified Likely benign in ECM1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-03). Ultra-rare (popmax 0.0981%, eas); Associated with ECM1-related disorder.

What condition is associated with ECM1 p.Tyr43= (c.129C>T)?

ECM1 p.Tyr43= (c.129C>T) is associated with ECM1-related disorder (ClinVar).

How common is ECM1 p.Tyr43= (c.129C>T) in the general population?

ECM1 p.Tyr43= (c.129C>T) is ultra-rare (popmax 0.0981%, eas) (gnomAD).

ECM1 p.Tyr43=

c.129C>T · rs201295989 · VCV3058755

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0981%, eas)

Conditions

ECM1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.21	GERP -2, phastCons 0.71
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0981% East Asian · 44/44,850 alleles

Filtering AF 0.075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0669%

Overall 0.00762% 123/1,613,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0981%	1,019
Middle Eastern	0.066%	1,515
African / African-American	0.0107%	9,368
Remaining individualsnot grpmax-eligible	0.008%	12,499
South Asian	0.00549%	18,217
European (non-Finnish)	0.00458%	21,848
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00333%	29,996

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.Tyr43=
Coding: c.129C>T
MANE Select: NM_004425
dbSNP: rs201295989
Type: single nucleotide variant
Location: chr1:150509668 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.05
Residue 43: the 'disordered' region

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

Disease context

ECM1-related disorder

Similar variants

ECM1 p.Arg476Ter Pathogenic/Likely pathogenic ★★ same condition
ECM1 p.Ser293= 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.Arg171fs Pathogenic ★ same condition
ECM1 p.Gln81fs Likely 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-tyr43 (accessed [today's date]).

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