Is PDE3A p.Val398= (c.1194C>T) pathogenic?

PDE3A p.Val398= (c.1194C>T) is classified Benign in PDE3A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with brachydactyly-arterial hypertension syndrome.

What condition is associated with PDE3A p.Val398= (c.1194C>T)?

PDE3A p.Val398= (c.1194C>T) is associated with brachydactyly-arterial hypertension syndrome (ClinVar).

PDE3A p.Val398=

Q: How common is PDE3A p.Val398= (c.1194C>T) in the general population?

PDE3A p.Val398= (c.1194C>T) is common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1194C>T · rs10743380 · VCV1226725

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

brachydactyly-arterial hypertension syndrome

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 -5.3	GERP -3.7
Overall
CADD	0.235	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99.8% East Asian · 44,793/44,862 alleles

Filtering AF 99.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.8%

Overall 93% 1,499,910/1,613,638 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	99.8%	1
Finnishnot grpmax-eligible	96%	1
Admixed American	94.3%	1
Amishnot grpmax-eligible	93.6%	1
European (non-Finnish)	93.4%	1
Ashkenazi Jewishnot grpmax-eligible	93.1%	1
Remaining individualsnot grpmax-eligible	92.6%	1
South Asian	92%	1
Middle Eastern	89.8%	1
African / African-American	80.4%	1

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.Val398=
Coding: c.1194C>T
MANE Select: NM_000921
dbSNP: rs10743380
Type: single nucleotide variant
Location: chr12:20613625 (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

Disease context

brachydactyly-arterial hypertension syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE3A p.Val398Ile Uncertain significance ★ ⚠ same residue
PDE3A p.Arg424His Uncertain significance ★★ ⚠ same condition
PDE3A p.Glu648Val Uncertain significance ★★ ⚠ same condition
PDE3A p.Pro430Leu Uncertain significance ★★ ⚠ same condition
PDE3A p.Thr383Lys Uncertain significance ★★ ⚠ same condition
PDE3A c.1760+38A>C Benign ★★ same condition
PDE3A c.2769+30C>T Benign ★★ same condition
PDE3A c.2925+15T>C Benign ★★ same condition

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-val398 (accessed [today's date]).

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