Is PDE4D p.Pro80= (c.240C>A) pathogenic?

PDE4D p.Pro80= (c.240C>A) is classified Likely benign in PDE4D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-27). Very rare (popmax 0.00469%, afr).

How common is PDE4D p.Pro80= (c.240C>A) in the general population?

PDE4D p.Pro80= (c.240C>A) is very rare (popmax 0.00469%, afr) (gnomAD).

PDE4D p.Pro80=

c.240C>A · VCV3612167

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00469%, afr)

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 -0.6	GERP -3
Overall
CADD	3.526	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00469% African / African-American · 3/63,934 alleles

Filtering AF 0.00125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000645%

Overall 0.00103% 13/1,260,178 alleles · very rare exomes 10/1,111,388 · genomes 3/148,790 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00469%	21,311
Admixed American	0.00395%	25,324
East Asian	0.00326%	30,672
South Asian	0.00324%	30,832
Remaining individualsnot grpmax-eligible	0.00216%	46,262
European (non-Finnish)	0.000599%	166,993

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: PDE4D
Protein: p.Pro80=
Coding: c.240C>A
MANE Select: NM_001104631
Type: single nucleotide variant
Location: chr5:59893383 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.01 · 122 PDB
Residue 80: the 'disordered' region

Full PDE4D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE4D p.Pro80Ser Uncertain significance ★ ⚠ same residue
PDE4D p.Pro80_Leu81insPro Uncertain significance ★ same residue
PDE4D p.Ile678Thr Pathogenic ★★ same type
PDE4D p.Pro225Leu Pathogenic ★★ same type
PDE4D c.*4886A>C Uncertain significance ★★ same type
PDE4D p.Arg133Trp Uncertain significance ★★ ⚠ same type
PDE4D p.Arg151Gly Uncertain significance ★★ ⚠ same type
PDE4D p.Arg249Gln 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/pde4d-p-pro80 (accessed [today's date]).

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