Is STRADA p.Val277fs (c.828_853del) pathogenic?

STRADA p.Val277fs (c.828853del) is classified Pathogenic in STRADA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-02). Very rare (popmax 8.48e-05%, nfe); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Val277fs (c.828_853del)?

STRADA p.Val277fs (c.828_853del) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Val277fs (c.828_853del) in the general population?

STRADA p.Val277fs (c.828_853del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

STRADA p.Val277fs

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

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

c.828_853del · VCV3644079

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,780 alleles

Overall 6.85e-05% 1/1,459,782 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.Val277fs
Coding: c.828_853del
MANE Select: NM_001003787
Type: Deletion
Location: chr17:63706640 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 277: the protein kinase domain

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.Val277= Likely benign ★ same residue
STRADA p.Lys18fs Pathogenic ★ same condition
STRADA p.Phe53fs Pathogenic ★ same condition
STRADA p.Pro34fs Pathogenic ★ same condition
STRADA p.His342fs Uncertain significance ★ same condition
STRADA p.Ile382fs Uncertain significance ★ same condition
STRADA p.Phe53del Uncertain significance ★ same condition
STRADA p.Pro364fs 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-val277fs (accessed [today's date]).

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