Is STRADA p.Ser264Arg (c.792T>A) pathogenic?

STRADA p.Ser264Arg (c.792T>A) is classified Uncertain significance in STRADA (ClinVar, Single submitter, 3 submitters; last evaluated 2022-05-22). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

How common is STRADA p.Ser264Arg (c.792T>A) in the general population?

STRADA p.Ser264Arg (c.792T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STRADA p.Ser264Arg (c.792T>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

STRADA p.Ser264Arg

Q: What condition is associated with STRADA p.Ser264Arg (c.792T>A)?

STRADA p.Ser264Arg (c.792T>A) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy, polyhydramnios, epilepsy (ClinVar).

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

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

c.792T>A · rs1057519011 · VCV374250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 1% in STRADA
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -17.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -1.6, phastCons 0.47
Regional constraint	o/e 0.81	unconstrained · MANE · 25 kb · p 5.3e-06 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser264Arg
Coding: c.792T>A
MANE Select: NM_001003787
dbSNP: rs1057519011
Type: single nucleotide variant
Location: chr17:63706701 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 264: 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

Also linked: polyhydramnios epilepsy

For Polyhydramnios-megalencephaly-symptomatic epilepsy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

STRADA p.Ser264Thr 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
STRADA p.Arg13Leu 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-ser264arg (accessed [today's date]).

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