Is ADAMTS10 p.Pro201Arg (c.602C>G) pathogenic?

ADAMTS10 p.Pro201Arg (c.602C>G) is classified Uncertain significance in ADAMTS10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1613); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADAMTS10 p.Pro201Arg (c.602C>G)?

ADAMTS10 p.Pro201Arg (c.602C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ADAMTS10 p.Pro201Arg (c.602C>G) in the general population?

ADAMTS10 p.Pro201Arg (c.602C>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about ADAMTS10 p.Pro201Arg (c.602C>G)?

AlphaMissense predicts likely benign (score 0.1613) — an in-silico prediction, not a clinical call.

ADAMTS10 p.Pro201Arg

c.602C>G · VCV3266517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1613	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -6.29	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 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 4,705 bp · p 0.038 · regional, not allelic
Overall
CADD	22.3	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 0.000593% European (non-Finnish) · 7/1,180,022 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,186 alleles · very rare

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: ADAMTS10
Protein: p.Pro201Arg
Coding: c.602C>G
MANE Select: NM_030957
Type: single nucleotide variant
Location: chr19:8601136 (GRCh38)
Gene constraint: LOEUF 0.467 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.88

Full ADAMTS10 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

Similar variants

ADAMTS10 p.Pro201Ser Uncertain significance ★ ⚠ same residue
ADAMTS10 p.Pro201Leu Uncertain significance ★ ⚠ same residue
ADAMTS10 p.Pro201= Likely benign ★ same residue
ADAMTS10 c.894+5G>A Uncertain significance ★★ same condition
ADAMTS10 p.Ala13Thr Uncertain significance ★★ ⚠ same condition
ADAMTS10 p.Ala4Thr Uncertain significance ★★ ⚠ same condition
ADAMTS10 p.Arg1093Ser Uncertain significance ★★ ⚠ same condition
ADAMTS10 p.Arg226Cys 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/adamts10-p-pro201arg (accessed [today's date]).

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