Is PDE3A p.Trp203Arg (c.607T>C) pathogenic?

PDE3A p.Trp203Arg (c.607T>C) is classified Uncertain significance in PDE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.8453); Very rare (popmax 0.0017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PDE3A p.Trp203Arg (c.607T>C)?

PDE3A p.Trp203Arg (c.607T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PDE3A p.Trp203Arg (c.607T>C) in the general population?

PDE3A p.Trp203Arg (c.607T>C) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about PDE3A p.Trp203Arg (c.607T>C)?

AlphaMissense predicts likely pathogenic (score 0.8453) — an in-silico prediction, not a clinical call.

PDE3A p.Trp203Arg

c.607T>C · VCV4627194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8453 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8453	likely pathogenic
REVEL	0.321	indeterminate
SaProt	LLR -6.44	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 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 268 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	27.1	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 0.0017% European (non-Finnish) · 20/1,179,806 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0013% 21/1,613,092 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,990
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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: PDE3A
Protein: p.Trp203Arg
Coding: c.607T>C
MANE Select: NM_000921
Type: single nucleotide variant
Location: chr12:20369891 (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.Trp203Cys Uncertain significance ★ ⚠ same residue
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

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-trp203arg (accessed [today's date]).

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