Is PDE2A p.Ser313= (c.939C>T) pathogenic?

PDE2A p.Ser313= (c.939C>T) is classified Benign/Likely benign in PDE2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-26). Ultra-rare (popmax 0.0495%, mid).

How common is PDE2A p.Ser313= (c.939C>T) in the general population?

PDE2A p.Ser313= (c.939C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

PDE2A p.Ser313=

c.939C>T · rs141849669 · VCV1424027

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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	GERP -3.2
Overall
CADD	11.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,058 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.0398% 642/1,612,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.32%	76
Middle Easterngrpmax	0.0495%	2,019
European (non-Finnish)	0.0463%	2,159
Remaining individualsnot grpmax-eligible	0.0336%	2,973
South Asian	0.0319%	3,134
Admixed American	0.0217%	4,613
Finnishnot grpmax-eligible	0.0187%	5,335
East Asian	0.00669%	14,958
African / African-American	0.004%	25,011

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser313=
Coding: c.939C>T
MANE Select: NM_002599
dbSNP: rs141849669
Type: single nucleotide variant
Location: chr11:72589175 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 313: the gaf 2 domain; an α-helix

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-ser313 (accessed [today's date]).

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