Is ADAMTS2 p.Asp361= (c.1083T>C) pathogenic?

ADAMTS2 p.Asp361= (c.1083T>C) is classified Conflicting classifications of pathogenicity in ADAMTS2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0833%, amr); Associated with Ehlers-Danlos syndrome.

What condition is associated with ADAMTS2 p.Asp361= (c.1083T>C)?

ADAMTS2 p.Asp361= (c.1083T>C) is associated with Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, dermatosparaxis type (ClinVar).

How common is ADAMTS2 p.Asp361= (c.1083T>C) in the general population?

ADAMTS2 p.Asp361= (c.1083T>C) is ultra-rare (popmax 0.0833%, amr) (gnomAD).

ADAMTS2 p.Asp361=

c.1083T>C · rs150079799 · VCV389834

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0833%, amr)

Conditions

Ehlers-Danlos syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.082	GERP -3.8, phastCons 0.31
Overall
CADD	1.285	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0833% Admixed American · 50/60,030 alleles

Filtering AF 0.0648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0583%

Overall 0.0461% 744/1,614,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	910
Admixed Americangrpmax	0.0833%	1,201
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
European (non-Finnish)	0.0525%	1,906
Finnishnot grpmax-eligible	0.0125%	8,002
African / African-American	0.012%	8,338
South Asian	0.0022%	45,542

Amish 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: ADAMTS2
Protein: p.Asp361=
Coding: c.1083T>C
MANE Select: NM_014244
dbSNP: rs150079799
Type: single nucleotide variant
Location: chr5:179158772 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.59
Residue 361: a disulfide bond; the peptidase m12b domain

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

Disease context

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

Also linked: Ehlers-Danlos syndrome, dermatosparaxis type

Similar variants

ADAMTS2 c.2085+1G>T Likely pathogenic ★★ same condition
ADAMTS2 c.3088+1G>A Likely pathogenic ★★ same condition
ADAMTS2 c.688+1G>A Likely pathogenic ★★ same condition
ADAMTS2 c.688+2T>C Likely pathogenic ★★ same condition
ADAMTS2 p.Arg1030Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Arg980Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Cys659Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTS2 p.Gln225Ter 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-asp361 (accessed [today's date]).

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