Is PDE11A p.Asp707Val (c.2120A>T) pathogenic?

PDE11A p.Asp707Val (c.2120A>T) is classified Uncertain significance in PDE11A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1.

How common is PDE11A p.Asp707Val (c.2120A>T) in the general population?

PDE11A p.Asp707Val (c.2120A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE11A p.Asp707Val (c.2120A>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

PDE11A p.Asp707Val

c.2120A>T · VCV4566246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 1% in PDE11A
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -16.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 443 kb · p 0.73 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDE11A
Protein: p.Asp707Val
Coding: c.2120A>T
MANE Select: NM_016953
Type: single nucleotide variant
Location: chr2:177711802 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.12
Residue 707: the pdease domain

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

Similar variants

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
PDE11A p.Tyr658Cys Uncertain significance ★★ ⚠ same type
PDE11A c.1576+26C>T Benign ★★ 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-asp707val (accessed [today's date]).

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