Is PDE3A p.Pro601Thr (c.1801C>A) pathogenic?

PDE3A p.Pro601Thr (c.1801C>A) is classified Conflicting classifications of pathogenicity in PDE3A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0629); Rare (popmax 0.856%, afr).

How common is PDE3A p.Pro601Thr (c.1801C>A) in the general population?

PDE3A p.Pro601Thr (c.1801C>A) is rare (popmax 0.856%, afr) (gnomAD).

What do computational predictors say about PDE3A p.Pro601Thr (c.1801C>A)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

PDE3A p.Pro601Thr

c.1801C>A · rs151312475 · VCV776696

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.856%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP 0.13, phastCons 0.003
Regional constraint	o/e 1.14	unconstrained · MANE · 268 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	6.552	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 0.856% African / African-American · 641/74,858 alleles

Filtering AF 0.801% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.78%

Overall 0.044% 708/1,610,638 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.856%	117
Remaining individualsnot grpmax-eligible	0.0722%	1,385
Admixed American	0.0218%	4,578
Middle Eastern	0.0166%	6,034
South Asian	0.0011%	90,742
European (non-Finnish)	0.000594%	168,293

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.Pro601Thr
Coding: c.1801C>A
MANE Select: NM_000921
dbSNP: rs151312475
Type: single nucleotide variant
Location: chr12:20633733 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB
Residue 601: the 'disordered' region

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

Similar variants

PDE3A p.Pro601His Uncertain significance ★ ⚠ same residue
PDE3A p.Pro601Ser Uncertain significance ★ ⚠ same residue
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

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-pro601thr (accessed [today's date]).

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