Is PDE11A p.Arg659= (c.1977G>T) pathogenic?

PDE11A p.Arg659= (c.1977G>T) is classified Benign in PDE11A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 2.89%, afr).

How common is PDE11A p.Arg659= (c.1977G>T) in the general population?

PDE11A p.Arg659= (c.1977G>T) is low-frequency (popmax 2.89%, afr) (gnomAD).

PDE11A p.Arg659=

c.1977G>T · rs77341035 · VCV709193

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.89%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.039	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -3.8, phastCons 0.008
Overall
CADD	4.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.89% African / African-American · 2,162/74,934 alleles

Filtering AF 2.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.74%

Overall 0.161% 2,596/1,612,118 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.89%	35
Middle Eastern	0.397%	252
Admixed American	0.248%	403
Remaining individualsnot grpmax-eligible	0.235%	425
South Asian	0.00989%	10,116
European (non-Finnish)	0.00849%	11,783
Finnishnot grpmax-eligible	0.00625%	16,010
East Asian	0.00223%	44,852

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.Arg659=
Coding: c.1977G>T
MANE Select: NM_016953
dbSNP: rs77341035
Type: single nucleotide variant
Location: chr2:177727724 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.12
Residue 659: the pdease domain

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

Similar variants

PDE11A p.Arg659Gln Uncertain significance ★ ⚠ same residue
PDE11A p.Arg659Trp Uncertain significance ★ ⚠ same residue
PDE11A p.Ser604Ter Pathogenic/Likely pathogenic ★★ same type
PDE11A p.Arg329Ter Uncertain significance ★★ same type
PDE11A p.Arg867Trp Uncertain significance ★★ ⚠ same type
PDE11A p.Gln374Ter Uncertain significance ★★ same type
PDE11A p.Pro165Thr Uncertain significance ★★ ⚠ same type
PDE11A p.Pro893Gln 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/pde11a-p-arg659 (accessed [today's date]).

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