Is STRADA p.Asp427= (c.1281C>T) pathogenic?

STRADA p.Asp427= (c.1281C>T) is classified Likely benign in STRADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-27). Ultra-rare (popmax 0.0164%, mid); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Asp427= (c.1281C>T)?

STRADA p.Asp427= (c.1281C>T) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Asp427= (c.1281C>T) in the general population?

STRADA p.Asp427= (c.1281C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

STRADA p.Asp427=

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

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

c.1281C>T · rs758494527 · VCV1151388

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -4	GERP -3.1
Overall
CADD	2.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00428% 69/1,613,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.008%	12,495
Admixed American	0.005%	19,985
European (non-Finnish)	0.00492%	20,343
East Asian	0.00223%	44,894
South Asian	0.0011%	91,048

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.Asp427=
Coding: c.1281C>T
MANE Select: NM_001003787
dbSNP: rs758494527
Type: single nucleotide variant
Location: chr17:63703614 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 427: 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 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
STRADA p.Arg13Leu Uncertain significance ★★ ⚠ same condition
STRADA p.Arg13Trp 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-asp427 (accessed [today's date]).

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