Is PDE8B p.Pro61= (c.183C>G) pathogenic?

PDE8B p.Pro61= (c.183C>G) is classified Likely benign in PDE8B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). Very rare (popmax 8.82e-05%, nfe).

How common is PDE8B p.Pro61= (c.183C>G) in the general population?

PDE8B p.Pro61= (c.183C>G) is very rare (popmax 8.82e-05%, nfe) (gnomAD).

PDE8B p.Pro61=

c.183C>G · rs2531984853 · VCV1944124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.82e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -0.78, phastCons 0.96
Overall
CADD	12.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.82e-05% European (non-Finnish) · 1/1,134,114 alleles

Overall 6.65e-05% 1/1,504,674 alleles · very rare exomes 1/1,352,554 · genomes 0/152,120 · joint denominator

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: PDE8B
Protein: p.Pro61=
Coding: c.183C>G
MANE Select: NM_003719
dbSNP: rs2531984853
Type: single nucleotide variant
Location: chr5:77211108 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.88

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

Similar variants

PDE8B p.Pro61Thr Uncertain significance ★ ⚠ same residue
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

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-pro61 (accessed [today's date]).

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