Is ADAMTS17 p.Pro354= (c.1062G>A) pathogenic?

ADAMTS17 p.Pro354= (c.1062G>A) is classified Conflicting classifications of pathogenicity in ADAMTS17 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0942%, nfe); Associated with Weill-Marchesani 4 syndrome, recessive.

What condition is associated with ADAMTS17 p.Pro354= (c.1062G>A)?

ADAMTS17 p.Pro354= (c.1062G>A) is associated with Weill-Marchesani 4 syndrome, recessive (ClinVar).

How common is ADAMTS17 p.Pro354= (c.1062G>A) in the general population?

ADAMTS17 p.Pro354= (c.1062G>A) is ultra-rare (popmax 0.0942%, nfe) (gnomAD).

ADAMTS17 p.Pro354=

Q: How is Ichthyosis-short stature-brachydactyly-microspherophakia syndrome inherited?

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

c.1062G>A · rs145206425 · VCV315302

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0942%, nfe)

Conditions

Weill-Marchesani 4 syndrome, recessive

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 -20	GERP -3.8
Overall
CADD	0.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0942% European (non-Finnish) · 1,111/1,179,354 alleles

Filtering AF 0.0896% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0877%

Overall 0.0858% 1,385/1,613,368 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.115%	868
European (non-Finnish)grpmax	0.0942%	1,062
Middle Eastern	0.0825%	1,212
East Asian	0.0735%	1,360
African / African-American	0.0653%	1,530
Finnishnot grpmax-eligible	0.0641%	1,561
Admixed American	0.06%	1,667
South Asian	0.0417%	2,397

Remaining individuals 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: ADAMTS17
Protein: p.Pro354=
Coding: c.1062G>A
MANE Select: NM_139057
dbSNP: rs145206425
Type: single nucleotide variant
Location: chr15:100254149 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 354: a disulfide bond; the peptidase m12b domain

Full ADAMTS17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Weill-Marchesani 4 syndrome, recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ichthyosis-short stature-brachydactyly-microspherophakia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ADAMTS17 c.1576-1G>T Likely pathogenic ★★ same condition
ADAMTS17 p.Arg433Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTS17 p.Arg854Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTS17 c.2017-3T>C Uncertain significance ★★ same condition
ADAMTS17 c.2295+3A>G Uncertain significance ★★ same condition
ADAMTS17 c.79+3A>C Uncertain significance ★★ same condition
ADAMTS17 c.-69C>T Uncertain significance ★★ same condition
ADAMTS17 c.*1766G>A 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/adamts17-p-pro354 (accessed [today's date]).

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