Is PDE3A p.Ser446= (c.1338G>C) pathogenic?

PDE3A p.Ser446= (c.1338G>C) is classified Likely benign in PDE3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-19). Absent from gnomAD v4.1; Associated with PDE3A-related disorder.

What condition is associated with PDE3A p.Ser446= (c.1338G>C)?

PDE3A p.Ser446= (c.1338G>C) is associated with PDE3A-related disorder (ClinVar).

How common is PDE3A p.Ser446= (c.1338G>C) in the general population?

PDE3A p.Ser446= (c.1338G>C) is absent from gnomAD v4.1 (gnomAD).

PDE3A p.Ser446=

c.1338G>C · rs371501182 · VCV3040930

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PDE3A-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 -1.5	GERP -3.6
Overall
CADD	2.905	PHRED · no single calibrated threshold — expert panels disagree

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: PDE3A
Protein: p.Ser446=
Coding: c.1338G>C
MANE Select: NM_000921
dbSNP: rs371501182
Type: single nucleotide variant
Location: chr12:20616298 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB
Residue 446: the 'disordered' region

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

Disease context

PDE3A-related disorder

Similar variants

PDE3A p.Gly449Ser Likely pathogenic ★ ⚠ same condition
PDE3A p.Gly449Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
PDE3A p.Val1009Leu Uncertain significance ★ ⚠ same condition
PDE3A p.Ser511Thr Uncertain significance ⚠ same condition
PDE3A p.Thr1107Asn Uncertain significance ⚠ same condition
PDE3A c.2769+6T>G Likely benign same condition
PDE3A c.-6T>G Benign same condition
PDE3A p.Arg268Lys Uncertain significance ★★ ⚠ same type

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-ser446 (accessed [today's date]).

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