Is ADAMTS3 p.Phe560Ser (c.1679T>C) pathogenic?

ADAMTS3 p.Phe560Ser (c.1679T>C) is classified Uncertain significance in ADAMTS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely pathogenic (0.5812); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADAMTS3 p.Phe560Ser (c.1679T>C)?

ADAMTS3 p.Phe560Ser (c.1679T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ADAMTS3 p.Phe560Ser (c.1679T>C) in the general population?

ADAMTS3 p.Phe560Ser (c.1679T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAMTS3 p.Phe560Ser (c.1679T>C)?

AlphaMissense predicts likely pathogenic (score 0.5812) — an in-silico prediction, not a clinical call.

ADAMTS3 p.Phe560Ser

c.1679T>C · VCV3491026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5812 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5812	likely pathogenic
REVEL	0.387	indeterminate
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP -0.48, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 286 kb · p 0.14 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADAMTS3
Protein: p.Phe560Ser
Coding: c.1679T>C
MANE Select: NM_014243
Type: single nucleotide variant
Location: chr4:72313743 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.31
Residue 560: the tsp type-1 1 domain

Full ADAMTS3 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

ADAMTS3 p.Arg94Ter Pathogenic ★ same condition
ADAMTS3 p.Ala1166Val Uncertain significance ★ ⚠ same condition
ADAMTS3 p.Ala11Val Uncertain significance ★ ⚠ same condition
ADAMTS3 p.Ala251Glu Uncertain significance ★ ⚠ same condition
ADAMTS3 p.Ala251Val Uncertain significance ★ ⚠ same condition
ADAMTS3 p.Ala364Thr Uncertain significance ★ ⚠ same condition
ADAMTS3 p.Ala397Val Uncertain significance ★ ⚠ same condition
ADAMTS3 p.Ala495Thr 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/adamts3-p-phe560ser (accessed [today's date]).

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