Is ECEL1 p.Gly170fs (c.509del) pathogenic?

ECEL1 p.Gly170fs (c.509del) is classified Pathogenic in ECEL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-22). Very rare (popmax 8.63e-05%, nfe); Associated with distal arthrogryposis type 5D.

What condition is associated with ECEL1 p.Gly170fs (c.509del)?

ECEL1 p.Gly170fs (c.509del) is associated with distal arthrogryposis type 5D (ClinVar).

How common is ECEL1 p.Gly170fs (c.509del) in the general population?

ECEL1 p.Gly170fs (c.509del) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

How is Distal arthrogryposis type 5D inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ECEL1 p.Gly170fs

c.509del · rs1553567937 · VCV435023

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Conditions

distal arthrogryposis type 5D

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 2 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,158,900 alleles

Overall 0.000142% 2/1,407,450 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00358%	27,966
European (non-Finnish)grpmax	8.63e-05%	1,158,900

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ECEL1
Protein: p.Gly170fs
Coding: c.509del
MANE Select: NM_004826
dbSNP: rs1553567937
Type: Deletion
Location: chr2:232486145 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 170: a disulfide bond; the peptidase m13 domain

Full ECEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

distal arthrogryposis type 5D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Distal arthrogryposis type 5D (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

ECEL1 p.Gly27fs Pathogenic/Likely pathogenic ★★ same condition
ECEL1 p.Phe37fs Pathogenic ★★ same condition
ECEL1 p.Arg49_Ser50delinsPro Likely pathogenic ★ same condition
ECEL1 p.Gln348fs Pathogenic ★ same condition
ECEL1 p.Glu13fs Likely pathogenic ★ same condition
ECEL1 p.Gly133fs Likely pathogenic ★ same condition
ECEL1 p.Pro595_Asp596del Likely pathogenic ★ same condition
ECEL1 p.Val558fs 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/ecel1-p-gly170fs (accessed [today's date]).

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