Is PDE2A p.Thr604= (c.1812C>A) pathogenic?

PDE2A p.Thr604= (c.1812C>A) is classified Likely benign in PDE2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-04). Absent from gnomAD v4.1; Associated with PDE2A-related disorder.

What condition is associated with PDE2A p.Thr604= (c.1812C>A)?

PDE2A p.Thr604= (c.1812C>A) is associated with PDE2A-related disorder (ClinVar).

How common is PDE2A p.Thr604= (c.1812C>A) in the general population?

PDE2A p.Thr604= (c.1812C>A) is absent from gnomAD v4.1 (gnomAD).

PDE2A p.Thr604=

c.1812C>A · VCV3352280

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

PDE2A-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 1.3	GERP 1.3, phastCons 1
Overall
CADD	8.59	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: PDE2A
Protein: p.Thr604=
Coding: c.1812C>A
MANE Select: NM_002599
Type: single nucleotide variant
Location: chr11:72582483 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 604: a UniProt-annotated variant site (in iddpads); the pdease domain

Full PDE2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PDE2A-related disorder

Similar variants

PDE2A c.71+5798G>A Likely benign same condition
PDE2A c.1922+4C>T Uncertain significance ★★ same type
PDE2A p.Ala157Val Uncertain significance ★★ ⚠ same type
PDE2A p.Ala205Val Uncertain significance ★★ ⚠ same type
PDE2A p.Ala349Thr Uncertain significance ★★ ⚠ same type
PDE2A p.Arg226Cys Uncertain significance ★★ ⚠ same type
PDE2A p.Arg790Gln Uncertain significance ★★ ⚠ same type
PDE2A p.Asp34Glu 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/pde2a-p-thr604 (accessed [today's date]).

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