Is PDE2A p.Arg892His (c.2675G>A) pathogenic?

PDE2A p.Arg892His (c.2675G>A) is classified Uncertain significance in PDE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely pathogenic (0.6696); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PDE2A p.Arg892His (c.2675G>A)?

PDE2A p.Arg892His (c.2675G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PDE2A p.Arg892His (c.2675G>A) in the general population?

PDE2A p.Arg892His (c.2675G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about PDE2A p.Arg892His (c.2675G>A)?

AlphaMissense predicts likely pathogenic (score 0.6696) — an in-silico prediction, not a clinical call.

PDE2A p.Arg892His

c.2675G>A · rs1458590398 · VCV2475203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6696	likely pathogenic
REVEL	0.743	pathogenic-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 862 bp · p 0.11 · regional, not allelic
Overall
CADD	28.9	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 0.000169% European (non-Finnish) · 2/1,179,994 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,566 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.Arg892His
Coding: c.2675G>A
MANE Select: NM_002599
dbSNP: rs1458590398
Type: single nucleotide variant
Location: chr11:72577535 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 892: an α-helix; 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE2A p.Ala157Val Uncertain significance ★★ ⚠ same condition
PDE2A p.Ala205Val Uncertain significance ★★ ⚠ same condition
PDE2A p.Ala349Thr Uncertain significance ★★ ⚠ same condition
PDE2A p.Arg790Gln Uncertain significance ★★ ⚠ same condition
PDE2A p.Asp34Glu Uncertain significance ★★ ⚠ same condition
PDE2A p.Asp59Asn Uncertain significance ★★ ⚠ same condition
PDE2A p.Cys263Gly Uncertain significance ★★ ⚠ same condition
PDE2A p.Gln41Glu Uncertain significance ★★ ⚠ same condition

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-arg892his (accessed [today's date]).

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