Is PDE3A p.Ala241Pro (c.721G>C) pathogenic?

PDE3A p.Ala241Pro (c.721G>C) is classified Uncertain significance in PDE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.7577); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PDE3A p.Ala241Pro (c.721G>C)?

PDE3A p.Ala241Pro (c.721G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PDE3A p.Ala241Pro (c.721G>C) in the general population?

PDE3A p.Ala241Pro (c.721G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE3A p.Ala241Pro (c.721G>C)?

AlphaMissense predicts likely pathogenic (score 0.7577) — an in-silico prediction, not a clinical call.

PDE3A p.Ala241Pro

c.721G>C · VCV4627196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7577 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7577	likely pathogenic
REVEL	0.372	indeterminate
SaProt	LLR -6.46	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 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 268 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	28.4	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

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.Ala241Pro
Coding: c.721G>C
MANE Select: NM_000921
Type: single nucleotide variant
Location: chr12:20370005 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB

Full PDE3A 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

PDE3A p.Arg268Lys Uncertain significance ★★ ⚠ same condition
PDE3A p.Pro430Leu Uncertain significance ★★ ⚠ same condition
PDE3A p.Ser325Pro Uncertain significance ★★ ⚠ same condition
PDE3A p.Ser633Ile Uncertain significance ★★ ⚠ same condition
PDE3A p.Thr383Lys Uncertain significance ★★ ⚠ same condition
PDE3A p.Thr609Ser Uncertain significance ★★ ⚠ same condition
PDE3A p.Ala447Thr Pathogenic ★ ⚠ same condition
PDE3A p.Ala1097Glu 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/pde3a-p-ala241pro (accessed [today's date]).

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