Is ADAMTSL2 p.Pro83= (c.249G>A) pathogenic?

ADAMTSL2 p.Pro83= (c.249G>A) is classified Likely benign in ADAMTSL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-10). Ultra-rare (popmax 0.0119%, nfe); Associated with ADAMTSL2-related disorder.

What condition is associated with ADAMTSL2 p.Pro83= (c.249G>A)?

ADAMTSL2 p.Pro83= (c.249G>A) is associated with ADAMTSL2-related disorder (ClinVar).

How common is ADAMTSL2 p.Pro83= (c.249G>A) in the general population?

ADAMTSL2 p.Pro83= (c.249G>A) is ultra-rare (popmax 0.0119%, nfe) (gnomAD).

ADAMTSL2 p.Pro83=

c.249G>A · VCV3344616

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, nfe)

Conditions

ADAMTSL2-related disorder

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 -5.7	GERP -2.6
Overall
CADD	0.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% European (non-Finnish) · 140/1,180,030 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00964%

Overall 0.0102% 164/1,613,370 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0119%	8,429
Remaining individualsnot grpmax-eligible	0.0112%	8,929
South Asian	0.00988%	10,121
African / African-American	0.00666%	15,012
Admixed American	0.005%	20,011

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: ADAMTSL2
Protein: p.Pro83=
Coding: c.249G>A
MANE Select: NM_014694
Type: single nucleotide variant
Location: chr9:133538364 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.10
Residue 83: the tsp type-1 1 domain; a disulfide bond

Full ADAMTSL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ADAMTSL2-related disorder

Similar variants

ADAMTSL2 p.Pro83Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ADAMTSL2 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTSL2 p.Ser454Leu Uncertain significance ★★ ⚠ same condition
ADAMTSL2 c.233+5G>C Likely pathogenic ★ same condition
ADAMTSL2 p.Cys591Ter Likely pathogenic ★ same condition
ADAMTSL2 p.Gln332Ter Likely pathogenic ★ same condition
ADAMTSL2 p.Gly421Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
ADAMTSL2 p.Val67Met 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/adamtsl2-p-pro83 (accessed [today's date]).

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