Is ADAMTS17 p.Pro574Ser (c.1720C>T) pathogenic?

ADAMTS17 p.Pro574Ser (c.1720C>T) is classified Uncertain significance in ADAMTS17 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-23). AlphaMissense: likely benign (0.2572); Ultra-rare (popmax 0.0175%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADAMTS17 p.Pro574Ser (c.1720C>T)?

ADAMTS17 p.Pro574Ser (c.1720C>T) is associated with Inborn genetic diseases, Weill-Marchesani 4 syndrome, recessive (ClinVar).

How common is ADAMTS17 p.Pro574Ser (c.1720C>T) in the general population?

ADAMTS17 p.Pro574Ser (c.1720C>T) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

What do computational predictors say about ADAMTS17 p.Pro574Ser (c.1720C>T)?

AlphaMissense predicts likely benign (score 0.2572) — an in-silico prediction, not a clinical call.

ADAMTS17 p.Pro574Ser

c.1720C>T · rs200327256 · VCV315285

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2572 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2572	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 367 kb · p 0.00029 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% European (non-Finnish) · 206/1,180,042 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0141% 227/1,614,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0175%	5,728
Finnishnot grpmax-eligible	0.0156%	6,403
Remaining individualsnot grpmax-eligible	0.0096%	10,418
African / African-American	0.00666%	15,014

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.Pro574Ser
Coding: c.1720C>T
MANE Select: NM_139057
dbSNP: rs200327256
Type: single nucleotide variant
Location: chr15:100132008 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 574: a disulfide bond; the tsp type-1 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Weill-Marchesani 4 syndrome, recessive

Similar variants

ADAMTS17 p.Pro574= Uncertain significance ★ same residue
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

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-pro574ser (accessed [today's date]).

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