Is PDE3A p.Thr445del (c.1324ACC[3]) pathogenic?

PDE3A p.Thr445del (c.1324ACC[3]) is classified Likely pathogenic in PDE3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-28). Absent from gnomAD v4.1; Associated with brachydactyly-arterial hypertension syndrome.

What condition is associated with PDE3A p.Thr445del (c.1324ACC[3])?

PDE3A p.Thr445del (c.1324ACC[3]) is associated with brachydactyly-arterial hypertension syndrome (ClinVar).

How common is PDE3A p.Thr445del (c.1324ACC[3]) in the general population?

PDE3A p.Thr445del (c.1324ACC[3]) is absent from gnomAD v4.1 (gnomAD).

PDE3A p.Thr445del

c.1324ACC[3] · rs1592115698 · VCV690366

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,896)

Conditions

brachydactyly-arterial hypertension syndrome

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 12	GERP 1.8, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,896). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDE3A
Protein: p.Thr445del
Coding: c.1324ACC[3]
MANE Select: NM_000921
dbSNP: rs1592115698
Type: Microsatellite
Location: chr12:20616284 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB
Residue 445: a UniProt-annotated variant site (in htnb; increased 3',5'-cyclic-amp phosphodiesterase activity; increased function in camp-mediated signaling); a UniProt-annotated variant site (in htnb; increased phosphorylation at s-428 and s-438; increased affinity for 3',5'-cyclic-amp; no effect on protein reaction kinetics for 3',5'-cyclic-amp phosphodiesterase activity; increased 3',5'-cyclic-amp phosphodiesterase activity; no effect on inhibition by 3',5'-cyclic-gmp; changed function in camp-mediated signaling); a UniProt-annotated variant site (in htnb; increased 3',5'-cyclic-amp phosphodiesterase activity; changed function in camp-mediated signaling); the 'disordered' region

Full PDE3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

brachydactyly-arterial hypertension syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE3A p.Thr445Ala Pathogenic ⚠ same residue
PDE3A p.Thr445Asn Pathogenic same residue
PDE3A p.Thr445Ser Pathogenic ⚠ same residue
PDE3A p.Arg424His Uncertain significance ★★ ⚠ same condition
PDE3A p.Glu648Val Uncertain significance ★★ ⚠ same condition
PDE3A p.Pro430Leu Uncertain significance ★★ ⚠ same condition
PDE3A p.Thr383Lys Uncertain significance ★★ ⚠ same condition
PDE3A c.1760+38A>C 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/pde3a-p-thr445del (accessed [today's date]).

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