Is PDE3A p.Ala348= (c.1044C>T) pathogenic?

PDE3A p.Ala348= (c.1044C>T) is classified Likely benign in PDE3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Ultra-rare (popmax 0.0164%, mid).

How common is PDE3A p.Ala348= (c.1044C>T) in the general population?

PDE3A p.Ala348= (c.1044C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PDE3A p.Ala348=

c.1044C>T · rs779242729 · VCV2160102

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -13	GERP -3.7
Overall
CADD	1.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00353% 57/1,613,936 alleles · ultra-rare exomes 51/1,461,746 · genomes 6/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	0.00381%	26,221

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.Ala348=
Coding: c.1044C>T
MANE Select: NM_000921
dbSNP: rs779242729
Type: single nucleotide variant
Location: chr12:20613475 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.11 · 9 PDB

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

Similar variants

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
PDE3A p.Thr609Ser 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-ala348 (accessed [today's date]).

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