Is PDE11A p.Arg7fs (c.20_21del) pathogenic?

PDE11A p.Arg7fs (c.2021del) is classified Conflicting classifications of pathogenicity in PDE11A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-02-01). Rare (popmax 0.28%, nfe); Associated with pigmented nodular adrenocortical disease, primary, 2.

What condition is associated with PDE11A p.Arg7fs (c.20_21del)?

PDE11A p.Arg7fs (c.20_21del) is associated with pigmented nodular adrenocortical disease, primary, 2 (ClinVar).

How common is PDE11A p.Arg7fs (c.20_21del) in the general population?

PDE11A p.Arg7fs (c.20_21del) is rare (popmax 0.28%, nfe) (gnomAD).

PDE11A p.Arg7fs

c.20_21del · rs202117698 · VCV225432

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.28%, nfe)

Conditions

pigmented nodular adrenocortical disease, primary, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.3	GERP 1.2, phastCons 1
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.28% European (non-Finnish) · 3,302/1,179,956 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.269%

Overall 0.288% 4,650/1,614,002 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.35%	74
European (non-Finnish)grpmax	0.28%	357
Remaining individualsnot grpmax-eligible	0.25%	401
East Asian	0.198%	504
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
Middle Eastern	0.116%	865
South Asian	0.113%	884
Admixed American	0.075%	1,334
African / African-American	0.0493%	2,028

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PDE11A
Protein: p.Arg7fs
Coding: c.20_21del
MANE Select: NM_016953 · reported on NM_001077197
dbSNP: rs202117698
Type: Deletion
Location: chr2:178104443 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.12

Full PDE11A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pigmented nodular adrenocortical disease, primary, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE11A p.Ser757fs Pathogenic/Likely pathogenic ★★ same condition
PDE11A p.Ala246fs Likely pathogenic ★ same condition
PDE11A p.Lys119fs Likely pathogenic ★ same condition
PDE11A p.Ser424fs Likely pathogenic ★ same condition
PDE11A p.Cys554fs Conflicting classifications of pathogenicity ★ same condition
PDE11A p.Gln46fs Conflicting classifications of pathogenicity ★ same condition
PDE11A p.Gln686fs Uncertain significance ★ same condition
PDE11A p.Leu470fs Uncertain significance ★ same condition

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/pde11a-p-arg7fs (accessed [today's date]).

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