Is PDE2A p.Gly235Val (c.704G>T) pathogenic?

PDE2A p.Gly235Val (c.704G>T) is classified Uncertain significance in PDE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-13). AlphaMissense: likely pathogenic (0.9256); Very rare (popmax 8.72e-05%, nfe).

How common is PDE2A p.Gly235Val (c.704G>T) in the general population?

PDE2A p.Gly235Val (c.704G>T) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about PDE2A p.Gly235Val (c.704G>T)?

AlphaMissense predicts likely pathogenic (score 0.9256) — an in-silico prediction, not a clinical call.

PDE2A p.Gly235Val

c.704G>T · rs1306285489 · VCV1394879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9256	likely pathogenic
REVEL	0.343	indeterminate
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Pangolin	Δ0.38	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 88 kb · p 0.0075 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,880 alleles

Overall 7.15e-05% 1/1,399,198 alleles · very rare

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.Gly235Val
Coding: c.704G>T
MANE Select: NM_002599
dbSNP: rs1306285489
Type: single nucleotide variant
Location: chr11:72590244 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 235: 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-gly235val (accessed [today's date]).

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