Is STRADA p.Arg13Trp (c.37C>T) pathogenic?

STRADA p.Arg13Trp (c.37C>T) is classified Uncertain significance in STRADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-26). AlphaMissense: likely pathogenic (0.8218); Ultra-rare (popmax 0.0177%, nfe); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Arg13Trp (c.37C>T)?

STRADA p.Arg13Trp (c.37C>T) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Arg13Trp (c.37C>T) in the general population?

STRADA p.Arg13Trp (c.37C>T) is ultra-rare (popmax 0.0177%, nfe) (gnomAD).

What do computational predictors say about STRADA p.Arg13Trp (c.37C>T)?

AlphaMissense predicts likely pathogenic (score 0.8218) — an in-silico prediction, not a clinical call.

STRADA p.Arg13Trp

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

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

c.37C>T · rs35808156 · VCV536760

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0177%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
AlphaMissense	0.8218	likely pathogenic
REVEL	0.232	benign-leaning
SaProt	LLR -11.27	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 25 kb · p 5.3e-06 · regional, not allelic
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0177% European (non-Finnish) · 209/1,179,926 alleles

Filtering AF 0.0157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.015%

Overall 0.0152% 246/1,613,874 alleles · ultra-rare exomes 224/1,461,688 · genomes 22/152,186 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0328%	3,047
European (non-Finnish)grpmax	0.0177%	5,646
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Admixed American	0.00667%	14,991
South Asian	0.0022%	45,537
African / African-American	0.00133%	74,998

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg13Trp
Coding: c.37C>T
MANE Select: NM_001003787
dbSNP: rs35808156
Type: single nucleotide variant
Location: chr17:63726695 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB
Residue 13: a UniProt-annotated variant site (in)

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.Arg13Gln Uncertain significance ★★ same residue
STRADA p.Arg13Leu Uncertain significance ★★ ⚠ same residue
STRADA p.Arg13= Likely benign ★ 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

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-arg13trp (accessed [today's date]).

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