Is PDE1A p.Asn519Ser (c.1556A>G) pathogenic?

PDE1A p.Asn519Ser (c.1556A>G) is classified Uncertain significance in PDE1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). Absent from gnomAD v4.1.

How common is PDE1A p.Asn519Ser (c.1556A>G) in the general population?

PDE1A p.Asn519Ser (c.1556A>G) is absent from gnomAD v4.1 (gnomAD).

PDE1A p.Asn519Ser

c.1556A>G · VCV3887185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.134	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.21, phastCons 1
Overall
CADD	17.76	PHRED · no single calibrated threshold — expert panels disagree

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: PDE1A
Protein: p.Asn519Ser
Coding: c.1556A>G
MANE Select: NM_001363871
Type: single nucleotide variant
Location: chr2:182147113 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.12
Residue 519: the pdease domain

Full PDE1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE1A c.1004+24G>T Benign ★★ same type
PDE1A c.101+113C>T Benign ★★ same type
PDE1A c.1207+48G>C Benign ★★ same type
PDE1A c.1207+62A>T Benign ★★ same type
PDE1A c.1208-106T>C Benign ★★ same type
PDE1A c.1516+17841A>G Benign ★★ same type
PDE1A c.168-1739A>C Benign ★★ same type
PDE1A c.168-1806A>G 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/pde1a-p-asn519ser (accessed [today's date]).

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