Is PDE3B p.Ala20Ser (c.58G>T) pathogenic?

PDE3B p.Ala20Ser (c.58G>T) is classified Uncertain significance in PDE3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.0765); Absent from gnomAD v4.1.

How common is PDE3B p.Ala20Ser (c.58G>T) in the general population?

PDE3B p.Ala20Ser (c.58G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE3B p.Ala20Ser (c.58G>T)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

PDE3B p.Ala20Ser

c.58G>T · VCV3930041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,587,416)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.21	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 6.6	GERP 0.84, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 187 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	18.04	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,587,416). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDE3B
Protein: p.Ala20Ser
Coding: c.58G>T
MANE Select: NM_000922
Type: single nucleotide variant
Location: chr11:14644133 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.10 · 4 PDB
Residue 20: the 'disordered' region; the 'interaction with rapgef3' region

Full PDE3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP2R1 p.Gly450Arg Uncertain significance ★★ ⚠ same type
CYP2R1 p.Gly91Asp Uncertain significance ★★ ⚠ same type
CYP2R1 p.His381Arg Uncertain significance ★★ ⚠ same type
CYP2R1 p.Ile332Thr Uncertain significance ★★ ⚠ same type
CYP2R1 p.Met284Ile Uncertain significance ★★ ⚠ same type
CYP2R1 p.Pro36Leu Uncertain significance ★★ ⚠ same type
CYP2R1 p.Tyr431His Uncertain significance ★★ ⚠ same type
PDE3B p.Thr137Ala 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/pde3b-p-ala20ser (accessed [today's date]).

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