Is PDE2A p.Ser578= (c.1734C>T) pathogenic?

PDE2A p.Ser578= (c.1734C>T) is classified Likely benign in PDE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). Very rare (popmax 0.00892%, eas).

How common is PDE2A p.Ser578= (c.1734C>T) in the general population?

PDE2A p.Ser578= (c.1734C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

PDE2A p.Ser578=

c.1734C>T · rs776910306 · VCV2178567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

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 0.004	GERP -0.63, phastCons 0.039
Overall
CADD	5.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,838 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00223% 36/1,612,070 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,210
Remaining individualsnot grpmax-eligible	0.00641%	15,597
Admixed American	0.00334%	29,941
European (non-Finnish)	0.00204%	49,116
Finnishnot grpmax-eligible	0.00156%	63,926
South Asian	0.0011%	90,914

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PDE2A
Protein: p.Ser578=
Coding: c.1734C>T
MANE Select: NM_002599
dbSNP: rs776910306
Type: single nucleotide variant
Location: chr11:72582561 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 578: a UniProt-annotated variant site (in iddpads); the pdease domain

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

Similar variants

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
PDE2A p.Asp59Asn 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-ser578 (accessed [today's date]).

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