Is ADAMTS9 p.Pro82Ser (c.244C>T) pathogenic?

ADAMTS9 p.Pro82Ser (c.244C>T) is classified Uncertain significance in ADAMTS9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.086); Ultra-rare (popmax 0.0164%, mid).

How common is ADAMTS9 p.Pro82Ser (c.244C>T) in the general population?

ADAMTS9 p.Pro82Ser (c.244C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ADAMTS9 p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

ADAMTS9 p.Pro82Ser

c.244C>T · VCV3492160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -4.94	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 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 37 kb · p 0.37 · regional, not allelic
Overall
CADD	22.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Overall 0.000124% 2/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00134%	74,902

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: ADAMTS9
Protein: p.Pro82Ser
Coding: c.244C>T
MANE Select: NM_182920
Type: single nucleotide variant
Location: chr3:64686840 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 69.47

Full ADAMTS9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAMTS9 p.Ala1505Thr Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Ala737Thr Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Arg1175Ser Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Arg1604Cys Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Arg1724Gln Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Arg480Gln Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Arg920Trp Uncertain significance ★★ ⚠ same type
ADAMTS9 p.Arg956His Uncertain significance ★★ ⚠ same type

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/adamts9-p-pro82ser (accessed [today's date]).

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