Is ADAMTS2 p.Phe1009Ter (c.3026_3027delinsAA) pathogenic?

ADAMTS2 p.Phe1009Ter (c.30263027delinsAA) is classified Pathogenic in ADAMTS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). Absent from gnomAD; Associated with Ehlers-Danlos syndrome, dermatosparaxis type.

What condition is associated with ADAMTS2 p.Phe1009Ter (c.3026_3027delinsAA)?

ADAMTS2 p.Phe1009Ter (c.3026_3027delinsAA) is associated with Ehlers-Danlos syndrome, dermatosparaxis type (ClinVar).

How common is ADAMTS2 p.Phe1009Ter (c.3026_3027delinsAA) in the general population?

ADAMTS2 p.Phe1009Ter (c.3026_3027delinsAA) is absent from gnomAD (gnomAD).

How is Dermatosparaxis Ehlers-Danlos syndrome inherited?

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

ADAMTS2 p.Phe1009Ter

c.3026_3027delinsAA · rs2480148186 · VCV2026724

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Ehlers-Danlos syndrome, dermatosparaxis type

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 20 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.9	GERP -2.2

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADAMTS2
Protein: p.Phe1009Ter
Coding: c.3026_3027delinsAA
MANE Select: NM_014244
dbSNP: rs2480148186
Type: Indel
Location: chr5:179122705 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.59
Residue 1009: a disulfide bond; the tsp type-1 4 domain

Full ADAMTS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome, dermatosparaxis type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dermatosparaxis Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ADAMTS2 p.Phe1009= Likely benign ★★ same residue
ADAMTS2 p.Arg1016Leu Uncertain significance ★★ same condition
ADAMTS2 p.Gln1064fs Likely pathogenic ★ same condition
ADAMTS2 p.Leu20fs Likely pathogenic ★ same condition
ADAMTS2 p.Val848fs Likely pathogenic ★ same condition
ADAMTS2 p.Pro1177Phe Uncertain significance ★ same condition
ADAMTS2 p.Trp643Tyr Uncertain significance ★ same condition
ADAMTS2 p.Val245Ile Uncertain significance ★ 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/adamts2-p-phe1009ter (accessed [today's date]).

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