Is PDE2A p.Arg905Cys (c.2713C>T) pathogenic?

PDE2A p.Arg905Cys (c.2713C>T) is classified Uncertain significance in PDE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely pathogenic (0.8472); Ultra-rare (popmax 0.0164%, mid).

How common is PDE2A p.Arg905Cys (c.2713C>T) in the general population?

PDE2A p.Arg905Cys (c.2713C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about PDE2A p.Arg905Cys (c.2713C>T)?

AlphaMissense predicts likely pathogenic (score 0.8472) — an in-silico prediction, not a clinical call.

PDE2A p.Arg905Cys

c.2713C>T · rs767040419 · VCV1986280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8472 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8472	likely pathogenic
REVEL	0.496	indeterminate
SaProt	LLR -7.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 862 bp · p 0.11 · regional, not allelic
Overall
CADD	34.0	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00205% 33/1,613,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
South Asian	0.00659%	15,181
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,461
European (non-Finnish)	0.00178%	56,191
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Arg905Cys
Coding: c.2713C>T
MANE Select: NM_002599
dbSNP: rs767040419
Type: single nucleotide variant
Location: chr11:72577497 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 44 PDB
Residue 905: a β-strand; a UniProt-annotated variant site (in iddpads)

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

Similar variants

PDE2A p.Arg905Leu Uncertain significance ★ ⚠ same residue
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-arg905cys (accessed [today's date]).

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