Is PDE11A p.His736= (c.2208C>T) pathogenic?

PDE11A p.His736= (c.2208C>T) is classified Likely benign in PDE11A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-13). Very rare (popmax 0.00298%, nfe); Associated with PDE11A-related disorder.

What condition is associated with PDE11A p.His736= (c.2208C>T)?

PDE11A p.His736= (c.2208C>T) is associated with PDE11A-related disorder (ClinVar).

How common is PDE11A p.His736= (c.2208C>T) in the general population?

PDE11A p.His736= (c.2208C>T) is very rare (popmax 0.00298%, nfe) (gnomAD).

PDE11A p.His736=

c.2208C>T · rs199620084 · VCV3052905

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00298%, nfe)

Conditions

PDE11A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.083	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.054, phastCons 1
Overall
CADD	7.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00298% European (non-Finnish) · 35/1,174,044 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00192%

Overall 0.00249% 40/1,607,424 alleles · very rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.439%	228
European (non-Finnish)grpmax	0.00298%	33,544
Remaining individualsnot grpmax-eligible	0.00161%	62,252

Amish 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.His736=
Coding: c.2208C>T
MANE Select: NM_016953
dbSNP: rs199620084
Type: single nucleotide variant
Location: chr2:177701157 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.12
Residue 736: the pdease domain

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

Disease context

PDE11A-related disorder

Similar variants

PDE11A p.Asp259Asn Uncertain significance ★ ⚠ same condition
PDE11A p.Ter934Gln Uncertain significance same condition
PDE11A p.Trp38Ter Uncertain significance same condition
PDE11A p.Tyr780Ter Uncertain significance same condition
PDE11A p.Ala572= Likely benign same condition
PDE11A p.Ala678Thr Benign same condition
PDE11A p.Leu196= Likely benign same condition
PDE11A p.Thr51= Likely benign 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-his736 (accessed [today's date]).

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