Is ADAMTS17 p.Pro72Ala (c.214C>G) pathogenic?

ADAMTS17 p.Pro72Ala (c.214C>G) is classified Conflicting classifications of pathogenicity in ADAMTS17 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0593); Ultra-rare (popmax 0.0803%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADAMTS17 p.Pro72Ala (c.214C>G)?

ADAMTS17 p.Pro72Ala (c.214C>G) is associated with Inborn genetic diseases, Weill-Marchesani 4 syndrome, recessive (ClinVar).

How common is ADAMTS17 p.Pro72Ala (c.214C>G) in the general population?

ADAMTS17 p.Pro72Ala (c.214C>G) is ultra-rare (popmax 0.0803%, nfe) (gnomAD).

What do computational predictors say about ADAMTS17 p.Pro72Ala (c.214C>G)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

ADAMTS17 p.Pro72Ala

c.214C>G · rs946108501 · VCV887944

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0803%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.66	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 5.3	GERP 0.62, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 367 kb · p 0.00029 · regional, not allelic
Overall
CADD	15.51	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0803% European (non-Finnish) · 768/956,946 alleles

Filtering AF 0.0755% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0737%

Overall 0.0703% 828/1,177,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0858%	1,165
European (non-Finnish)grpmax	0.0803%	1,246
Remaining individualsnot grpmax-eligible	0.0586%	1,707
Middle Eastern	0.0348%	2,876
African / African-American	0.0163%	6,148
Admixed American	0.00932%	10,731

Finnish 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.Pro72Ala
Coding: c.214C>G
MANE Select: NM_139057
dbSNP: rs946108501
Type: single nucleotide variant
Location: chr15:100341275 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.06
Residue 72: the 'disordered' region

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.Pro72Thr Uncertain significance ★★ ⚠ same residue
ADAMTS17 p.Pro72Arg Uncertain significance ★ ⚠ same residue
ADAMTS17 p.Pro72= Likely benign ★ 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

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-pro72ala (accessed [today's date]).

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