Is PDE3A p.Ser1030= (c.3090C>T) pathogenic?

PDE3A p.Ser1030= (c.3090C>T) is classified Benign/Likely benign in PDE3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-30). Low-frequency (popmax 1.42%, eas).

How common is PDE3A p.Ser1030= (c.3090C>T) in the general population?

PDE3A p.Ser1030= (c.3090C>T) is low-frequency (popmax 1.42%, eas) (gnomAD).

PDE3A p.Ser1030=

c.3090C>T · rs142569377 · VCV1604887

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3.9
Overall
CADD	6.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% East Asian · 635/44,862 alleles

Filtering AF 1.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.29%

Overall 0.045% 726/1,613,834 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.42%	71
Remaining individualsnot grpmax-eligible	0.0608%	1,645
South Asian	0.0253%	3,960
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,922
African / African-American	0.00933%	10,713
Admixed American	0.00167%	60,002
European (non-Finnish)	0.00144%	69,402

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: PDE3A
Protein: p.Ser1030=
Coding: c.3090C>T
MANE Select: NM_000921
dbSNP: rs142569377
Type: single nucleotide variant
Location: chr12:20654111 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB
Residue 1030: the 'interaction with slfn12' region; the 'disordered' region; the pdease domain

Full PDE3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE3A p.Ser1030Gly Uncertain significance ★ ⚠ same residue
PDE3A p.Arg268Lys Uncertain significance ★★ ⚠ same type
PDE3A p.Arg424His Uncertain significance ★★ ⚠ same type
PDE3A p.Glu648Val Uncertain significance ★★ ⚠ same type
PDE3A p.Pro430Leu Uncertain significance ★★ ⚠ same type
PDE3A p.Ser325Pro Uncertain significance ★★ ⚠ same type
PDE3A p.Ser633Ile Uncertain significance ★★ ⚠ same type
PDE3A p.Thr383Lys Uncertain significance ★★ ⚠ 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/pde3a-p-ser1030 (accessed [today's date]).

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