Is STRADA p.Met83del (c.245TGA[1]) pathogenic?

STRADA p.Met83del (c.245TGA[1]) is classified Uncertain significance in STRADA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-25). Very rare (popmax 0.000424%, nfe); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Met83del (c.245TGA[1])?

STRADA p.Met83del (c.245TGA[1]) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Met83del (c.245TGA[1]) in the general population?

STRADA p.Met83del (c.245TGA[1]) is very rare (popmax 0.000424%, nfe) (gnomAD).

STRADA p.Met83del

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

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

c.245TGA[1] · rs1255799252 · VCV1040839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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 · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,008 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,796 alleles · very rare

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.Met83del
Coding: c.245TGA[1]
MANE Select: NM_001003787
dbSNP: rs1255799252
Type: Microsatellite
Location: chr17:63713504 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 83: the protein kinase domain; a β-strand

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.Val85fs Pathogenic ★ same condition
STRADA c.1101-16_1101-14del Likely benign ★ same condition
STRADA c.1101-23TC[2] Likely benign ★ same condition
STRADA c.124-15CTTTTT[3] Likely benign ★ same condition
STRADA c.36+20_36+22del Likely benign ★ same condition
STRADA c.858+12_858+14del Likely benign ★ same condition
STRADA c.36+1G>A Likely pathogenic ★★ same condition
STRADA c.37-1G>C Likely pathogenic ★★ 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-met83del (accessed [today's date]).

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