Is PDE1A p.Arg87Gln (c.260G>A) pathogenic?

PDE1A p.Arg87Gln (c.260G>A) is classified Uncertain significance in PDE1A (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-28). AlphaMissense: likely benign (0.1621); Ultra-rare (popmax 0.011%, sas).

How common is PDE1A p.Arg87Gln (c.260G>A) in the general population?

PDE1A p.Arg87Gln (c.260G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about PDE1A p.Arg87Gln (c.260G>A)?

AlphaMissense predicts likely benign (score 0.1621) — an in-silico prediction, not a clinical call.

PDE1A p.Arg87Gln

c.260G>A · rs761155078 · VCV2590166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1621 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1621	likely benign
REVEL	0.439	indeterminate
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R103Q vs ClinVar R87Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,028 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00223% 36/1,613,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,103
Admixed American	0.005%	19,995
African / African-American	0.00401%	24,954
European (non-Finnish)	0.0017%	58,992

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: PDE1A
Protein: p.Arg87Gln
Coding: c.260G>A
MANE Select: NM_001363871
dbSNP: rs761155078
Type: single nucleotide variant
Location: chr2:182240200 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.12

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

Similar variants

PDE1A p.Arg87Trp Uncertain significance ★ ⚠ same residue
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

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-arg87gln (accessed [today's date]).

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