Is ADAMTS3 p.Ser19= (c.57A>G) pathogenic?

ADAMTS3 p.Ser19= (c.57A>G) is classified Likely benign in ADAMTS3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-01). Rare (popmax 0.23%, mid); Associated with ADAMTS3-related disorder.

What condition is associated with ADAMTS3 p.Ser19= (c.57A>G)?

ADAMTS3 p.Ser19= (c.57A>G) is associated with ADAMTS3-related disorder (ClinVar).

How common is ADAMTS3 p.Ser19= (c.57A>G) in the general population?

ADAMTS3 p.Ser19= (c.57A>G) is rare (popmax 0.23%, mid) (gnomAD).

ADAMTS3 p.Ser19=

c.57A>G · rs151177298 · VCV3056027

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.23%, mid)

Conditions

ADAMTS3-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 0.44	GERP 1.3, phastCons 1
Overall
CADD	9.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.23% Middle Eastern · 14/6,082 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00973% 157/1,613,360 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.23%	434
Admixed American	0.0267%	3,744
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,399
Remaining individualsnot grpmax-eligible	0.0128%	7,808
European (non-Finnish)	0.00949%	10,534
African / African-American	0.00401%	24,921

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: ADAMTS3
Protein: p.Ser19=
Coding: c.57A>G
MANE Select: NM_014243
dbSNP: rs151177298
Type: single nucleotide variant
Location: chr4:72568706 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.31

Full ADAMTS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ADAMTS3-related disorder

Similar variants

ADAMTS3 p.Ser19Ala Uncertain significance ★ ⚠ same residue
ADAMTS3 p.Pro460Leu Uncertain significance ⚠ same condition
ADAMTS3 p.Gly273= Benign same condition
ADAMTS3 p.His111Tyr Benign same condition
ADAMTS3 p.Pro513Thr Benign same condition
ADAMTS3 p.Thr133= Likely benign same condition
ADAMTS3 p.Thr797= Likely benign same condition
ADAMTS3 p.Tyr659= Likely benign 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/adamts3-p-ser19 (accessed [today's date]).

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