Is PDE4B p.Ser384Pro (c.1150T>C) pathogenic?

PDE4B p.Ser384Pro (c.1150T>C) is classified Uncertain significance in PDE4B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely benign (0.068); Absent from gnomAD v4.1.

How common is PDE4B p.Ser384Pro (c.1150T>C) in the general population?

PDE4B p.Ser384Pro (c.1150T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE4B p.Ser384Pro (c.1150T>C)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

PDE4B p.Ser384Pro

c.1150T>C · VCV3416254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -3.02	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 6.2	GERP 5.8, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 40 kb · p 9.4e-25 · regional, not allelic
Overall
CADD	19.43	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

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: PDE4B
Protein: p.Ser384Pro
Coding: c.1150T>C
MANE Select: NM_002600
Type: single nucleotide variant
Location: chr1:66363437 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.22 · 43 PDB
Residue 384: the pdease domain

Full PDE4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE4B p.Arg596= Benign ★★ same type
PDE4B p.Leu642= Benign ★★ same type
PDE4B p.Ser703Cys Benign ★★ same type
PDE4B p.Ala148Val Uncertain significance ★ ⚠ same type
PDE4B p.Arg130Cys Uncertain significance ★ ⚠ same type
PDE4B p.Arg503Cys Uncertain significance ★ ⚠ same type
PDE4B p.Arg552His Uncertain significance ★ ⚠ same type
PDE4B p.Arg576Pro 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/pde4b-p-ser384pro (accessed [today's date]).

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