Is PDE4A p.Arg799Pro (c.2396G>C) pathogenic?

PDE4A p.Arg799Pro (c.2396G>C) is classified Likely benign in PDE4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.0864); Ultra-rare (popmax 0.0266%, afr).

How common is PDE4A p.Arg799Pro (c.2396G>C) in the general population?

PDE4A p.Arg799Pro (c.2396G>C) is ultra-rare (popmax 0.0266%, afr) (gnomAD).

What do computational predictors say about PDE4A p.Arg799Pro (c.2396G>C)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

PDE4A p.Arg799Pro

c.2396G>C · VCV3416248

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0266%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -4.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.097	GERP -3.9
Regional constraint	o/e 0.99	unconstrained · MANE · 574 bp · p 0.85 · regional, not allelic
Overall
CADD	0.101	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0266% African / African-American · 20/75,058 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00136% 22/1,614,170 alleles · ultra-rare exomes 16/1,461,888 · genomes 6/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0266%	3,753
Remaining individualsnot grpmax-eligible	0.0032%	31,255

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: PDE4A
Protein: p.Arg799Pro
Coding: c.2396G>C
MANE Select: NM_001111307
Type: single nucleotide variant
Location: chr19:10467356 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.87 · 5 PDB

Full PDE4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE4A p.Ala590= Benign ★★ same type
PDE4A p.Arg20= Benign ★★ same type
PDE4A p.Arg608= Benign ★★ same type
PDE4A p.Glu732Gly Benign ★★ same type
PDE4A p.Pro331Ser Benign/Likely benign ★★ same type
PDE4A p.Ser279= Benign ★★ same type
PDE4A c.620+2T>C Uncertain significance ★ same type
PDE4A p.Ala428Thr 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/pde4a-p-arg799pro (accessed [today's date]).

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