Is PDE1C p.Arg294Ser (c.882A>C) pathogenic?

PDE1C p.Arg294Ser (c.882A>C) is classified Uncertain significance in PDE1C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely pathogenic (0.9654); Absent from gnomAD v4.1.

How common is PDE1C p.Arg294Ser (c.882A>C) in the general population?

PDE1C p.Arg294Ser (c.882A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE1C p.Arg294Ser (c.882A>C)?

AlphaMissense predicts likely pathogenic (score 0.9654) — an in-silico prediction, not a clinical call.

PDE1C p.Arg294Ser

c.882A>C · rs1792851728 · VCV3210653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9654 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9654	likely pathogenic
REVEL	0.572	indeterminate
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP -0.1, phastCons 0.002
Regional constraint	o/e 0.69	unconstrained · MANE · 41 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

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: PDE1C
Protein: p.Arg294Ser
Coding: c.882A>C
MANE Select: NM_001191057
dbSNP: rs1792851728
Type: single nucleotide variant
Location: chr7:31848066 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.53
Residue 294: the pdease domain

Full PDE1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE1C p.Arg45Gln Uncertain significance ★★ ⚠ same type
PDE1C p.His619Tyr Uncertain significance ★★ ⚠ same type
PPP1R17 p.Asp21Glu Uncertain significance ★★ ⚠ same type
PPP1R17 p.Gln8Arg Uncertain significance ★★ ⚠ same type
PDE1C c.1203+28A>G Benign ★★ same type
PDE1C p.Ala594= Benign ★★ same type
PDE1C p.Arg635His Likely benign ★★ same type
PDE1C p.Arg660His 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/pde1c-p-arg294ser (accessed [today's date]).

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