Is PDE3A p.Arg862Cys (c.2584C>T) pathogenic?

PDE3A p.Arg862Cys (c.2584C>T) is classified Uncertain significance in PDE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). AlphaMissense: likely pathogenic (0.9037); Absent from gnomAD v4.1.

How common is PDE3A p.Arg862Cys (c.2584C>T) in the general population?

PDE3A p.Arg862Cys (c.2584C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE3A p.Arg862Cys (c.2584C>T)?

AlphaMissense predicts likely pathogenic (score 0.9037) — an in-silico prediction, not a clinical call.

PDE3A p.Arg862Cys

c.2584C>T · rs1944835888 · VCV2793896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9037 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9037	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -12.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 17 kb · p 6.8e-13 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDE3A
Protein: p.Arg862Cys
Coding: c.2584C>T
MANE Select: NM_000921
dbSNP: rs1944835888
Type: single nucleotide variant
Location: chr12:20648706 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB
Residue 862: the 'interaction with slfn12' region; the pdease domain

Full PDE3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE3A p.Arg268Lys Uncertain significance ★★ ⚠ same type
PDE3A p.Arg424His Uncertain significance ★★ ⚠ same type
PDE3A p.Glu648Val Uncertain significance ★★ ⚠ same type
PDE3A p.Pro430Leu Uncertain significance ★★ ⚠ same type
PDE3A p.Ser325Pro Uncertain significance ★★ ⚠ same type
PDE3A p.Ser633Ile Uncertain significance ★★ ⚠ same type
PDE3A p.Thr383Lys Uncertain significance ★★ ⚠ same type
PDE3A p.Thr609Ser 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/pde3a-p-arg862cys (accessed [today's date]).

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