Is PDE8B p.Arg714= (c.2140C>A) pathogenic?

PDE8B p.Arg714= (c.2140C>A) is classified Likely benign in PDE8B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-19). Absent from gnomAD v4.1.

How common is PDE8B p.Arg714= (c.2140C>A) in the general population?

PDE8B p.Arg714= (c.2140C>A) is absent from gnomAD v4.1 (gnomAD).

PDE8B p.Arg714=

c.2140C>A · rs1346301868 · VCV1947409

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 2.2, phastCons 1
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

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: PDE8B
Protein: p.Arg714=
Coding: c.2140C>A
MANE Select: NM_003719
dbSNP: rs1346301868
Type: single nucleotide variant
Location: chr5:77419777 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.88
Residue 714: the pdease domain

Full PDE8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE8B c.*498C>A Uncertain significance ★★ same type
PDE8B p.Ala232Ser Uncertain significance ★★ ⚠ same type
PDE8B p.Ala4Val Uncertain significance ★★ ⚠ same type
PDE8B p.Ala65Pro Uncertain significance ★★ ⚠ same type
PDE8B p.Ala70Ser Uncertain significance ★★ ⚠ same type
PDE8B p.Ala86Thr Uncertain significance ★★ ⚠ same type
PDE8B p.Arg237Lys Uncertain significance ★★ ⚠ same type
PDE8B p.Arg483Trp 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/pde8b-p-arg714 (accessed [today's date]).

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