Is STRADA p.Pro364= (c.1092G>A) pathogenic?

STRADA p.Pro364= (c.1092G>A) is classified Likely benign in STRADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.0134%, eas); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Pro364= (c.1092G>A)?

STRADA p.Pro364= (c.1092G>A) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Pro364= (c.1092G>A) in the general population?

STRADA p.Pro364= (c.1092G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

STRADA p.Pro364=

Q: How is Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1092G>A · rs768049874 · VCV742195

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

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 -9.9	GERP -3.6
Overall
CADD	1.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,790 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.00161% 26/1,611,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,465
South Asian	0.00661%	15,126
Admixed American	0.00502%	19,925
Remaining individualsnot grpmax-eligible	0.00481%	20,793
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,522
African / African-American	0.00134%	74,752
European (non-Finnish)	0.000509%	196,566

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: STRADA
Protein: p.Pro364=
Coding: c.1092G>A
MANE Select: NM_001003787
dbSNP: rs768049874
Type: single nucleotide variant
Location: chr17:63704349 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 364: the protein kinase domain; a turn

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

Disease context

polyhydramnios, megalencephaly, and symptomatic epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

STRADA p.Pro364Arg Uncertain significance ★★ ⚠ same residue
STRADA p.Pro364Ala Uncertain significance ★ ⚠ same residue
STRADA p.Pro364Leu Uncertain significance ★ ⚠ same residue
STRADA p.Pro364fs Uncertain significance ★ same residue
STRADA c.36+1G>A Likely pathogenic ★★ same condition
STRADA c.37-1G>C Likely pathogenic ★★ same condition
STRADA p.Arg228Ter Pathogenic ★★ same condition
STRADA p.Ala45Val Uncertain significance ★★ ⚠ 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/strada-p-pro364 (accessed [today's date]).

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