Is STRADA p.Pro350= (c.1050C>G) pathogenic?

STRADA p.Pro350= (c.1050C>G) is classified Likely benign in STRADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0454%, afr); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Pro350= (c.1050C>G)?

STRADA p.Pro350= (c.1050C>G) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Pro350= (c.1050C>G) in the general population?

STRADA p.Pro350= (c.1050C>G) is ultra-rare (popmax 0.0454%, afr) (gnomAD).

STRADA p.Pro350=

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

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

c.1050C>G · rs370096068 · VCV436886

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0454%, afr)

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 0.14	GERP -3.6, phastCons 0.86
Overall
CADD	7.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0454% African / African-American · 34/74,908 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.00459% 74/1,612,654 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0454%	2,203
Finnishnot grpmax-eligible	0.00786%	12,726
Remaining individualsnot grpmax-eligible	0.00641%	15,603
South Asian	0.0033%	30,309
European (non-Finnish)	0.00229%	43,690
Admixed American	0.00167%	59,854

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.Pro350=
Coding: c.1050C>G
MANE Select: NM_001003787
dbSNP: rs370096068
Type: single nucleotide variant
Location: chr17:63704391 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 350: the protein kinase domain; an α-helix

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.Pro350His Uncertain significance ★★ ⚠ same residue
STRADA p.Pro350Ser 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
STRADA p.Arg100Gln Uncertain significance ★★ ⚠ same condition
STRADA p.Arg13Gln 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-pro350 (accessed [today's date]).

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