Is PDE4B p.Arg130Cys (c.388C>T) pathogenic?

PDE4B p.Arg130Cys (c.388C>T) is classified Uncertain significance in PDE4B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.9837); Very rare (popmax 0.00224%, eas).

How common is PDE4B p.Arg130Cys (c.388C>T) in the general population?

PDE4B p.Arg130Cys (c.388C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about PDE4B p.Arg130Cys (c.388C>T)?

AlphaMissense predicts likely pathogenic (score 0.9837) — an in-silico prediction, not a clinical call.

PDE4B p.Arg130Cys

c.388C>T · rs772252118 · VCV3210713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9837	likely pathogenic
REVEL	0.837	moderately pathogenic-leaning
SaProt	LLR -13.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 419 kb · p 0.17 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.00224% East Asian · 1/44,714 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000931% 15/1,611,804 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,714
Admixed American	0.00167%	59,708
Remaining individualsnot grpmax-eligible	0.0016%	62,382
European (non-Finnish)	0.00102%	98,234

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: PDE4B
Protein: p.Arg130Cys
Coding: c.388C>T
MANE Select: NM_002600
dbSNP: rs772252118
Type: single nucleotide variant
Location: chr1:66247566 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.22 · 43 PDB

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.Arg503Cys Uncertain significance ★ ⚠ same type
PDE4B p.Arg552His Uncertain significance ★ ⚠ same type
PDE4B p.Arg576Pro Uncertain significance ★ ⚠ same type
PDE4B p.Arg581Cys 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-arg130cys (accessed [today's date]).

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