Is PDE4D p.Phe191= (c.573C>T) pathogenic?

PDE4D p.Phe191= (c.573C>T) is classified Likely benign in PDE4D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-11). Very rare (popmax 0.000763%, nfe).

How common is PDE4D p.Phe191= (c.573C>T) in the general population?

PDE4D p.Phe191= (c.573C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

PDE4D p.Phe191=

c.573C>T · VCV4729015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000763%, 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 2.7	GERP 4.2, phastCons 1
Overall
CADD	9.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,676 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,412 alleles · very rare

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.Phe191=
Coding: c.573C>T
MANE Select: NM_001104631
Type: single nucleotide variant
Location: chr5:59215851 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.01 · 122 PDB

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

Similar variants

PDE4D p.Phe191Val 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
PDE4D p.Arg727Trp 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-phe191 (accessed [today's date]).

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