Is AGPS p.Thr549del (c.1646_1648del) pathogenic?

AGPS p.Thr549del (c.16461648del) is classified Uncertain significance in AGPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-31). Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS p.Thr549del (c.1646_1648del)?

AGPS p.Thr549del (c.1646_1648del) is associated with rhizomelic chondrodysplasia punctata type 3 (ClinVar).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGPS p.Thr549del

c.1646_1648del · VCV4068716

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

rhizomelic chondrodysplasia punctata type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1

Variant & gene context

Gene: AGPS
Protein: p.Thr549del
Coding: c.1646_1648del
MANE Select: NM_003659
Type: Deletion
Location: chr2:177513855 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27

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

Disease context

rhizomelic chondrodysplasia punctata type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AGPS c.563-10del Benign ★★ same condition
AGPS c.1286delG Likely pathogenic ★ same condition
AGPS c.557_562+5del Likely pathogenic ★ same condition
AGPS p.Asn272fs Likely pathogenic ★ same condition
AGPS p.Glu306fs Likely pathogenic ★ same condition
AGPS p.Glu346fs Likely pathogenic ★ same condition
AGPS p.Glu520fs Likely pathogenic ★ same condition
AGPS p.Thr549Ala Uncertain significance ★ ⚠ same residue

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/agps-p-thr549del (accessed [today's date]).

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