Is STRADA p.Tyr210Ter (c.630C>G) pathogenic?

STRADA p.Tyr210Ter (c.630C>G) is classified Pathogenic in STRADA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). Absent from gnomAD v4.1; Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Tyr210Ter (c.630C>G)?

STRADA p.Tyr210Ter (c.630C>G) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Tyr210Ter (c.630C>G) in the general population?

STRADA p.Tyr210Ter (c.630C>G) is absent from gnomAD v4.1 (gnomAD).

STRADA p.Tyr210Ter

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

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

c.630C>G · rs2511074603 · VCV2749405

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 13
Splicing
SpliceAI	Δ0.41	acceptor loss · deltas
Pangolin	Δ0.40	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STRADA
Protein: p.Tyr210Ter
Coding: c.630C>G
MANE Select: NM_001003787
dbSNP: rs2511074603
Type: single nucleotide variant
Location: chr17:63707370 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 210: 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 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-tyr210ter (accessed [today's date]).

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