Is ADAMTS2 p.Ser232fs (c.693del) pathogenic?

ADAMTS2 p.Ser232fs (c.693del) is classified Likely pathogenic in ADAMTS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-28). Absent from gnomAD; Associated with Ehlers-Danlos syndrome, dermatosparaxis type.

What condition is associated with ADAMTS2 p.Ser232fs (c.693del)?

ADAMTS2 p.Ser232fs (c.693del) is associated with Ehlers-Danlos syndrome, dermatosparaxis type (ClinVar).

How common is ADAMTS2 p.Ser232fs (c.693del) in the general population?

ADAMTS2 p.Ser232fs (c.693del) 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.Ser232fs

c.693del · rs2480416655 · VCV1724168

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.14	GERP -3.2

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.Ser232fs
Coding: c.693del
MANE Select: NM_014244
dbSNP: rs2480416655
Type: Deletion
Location: chr5:179207711 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.59

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.Ser232= Likely benign ★ same residue
ADAMTS2 c.689-9_695del Likely pathogenic ★★ same condition
ADAMTS2 p.Ala89fs Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Met791fs Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Pro33fs Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Pro34fs Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Pro46fs Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Tyr834_Met835insTer Pathogenic/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/adamts2-p-ser232fs (accessed [today's date]).

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