Is STRADA p.Arg13Gln (c.38G>A) pathogenic?

STRADA p.Arg13Gln (c.38G>A) is classified Uncertain significance in STRADA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-17). AlphaMissense: ambiguous (0.4524); Ultra-rare (popmax 0.0579%, eas); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Arg13Gln (c.38G>A)?

STRADA p.Arg13Gln (c.38G>A) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Arg13Gln (c.38G>A) in the general population?

STRADA p.Arg13Gln (c.38G>A) is ultra-rare (popmax 0.0579%, eas) (gnomAD).

What do computational predictors say about STRADA p.Arg13Gln (c.38G>A)?

AlphaMissense predicts ambiguous (score 0.4524) — an in-silico prediction, not a clinical call.

STRADA p.Arg13Gln

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

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

c.38G>A · rs528919447 · VCV863115

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4524 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0579%, eas)

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
AlphaMissense	0.4524	ambiguous
REVEL	0.3	indeterminate
SaProt	LLR -6.76	tolerated
Splicing
SpliceAI	Δ0.90	acceptor gain · deltas
Pangolin	Δ0.60	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 25 kb · p 5.3e-06 · regional, not allelic
Overall
CADD	37.0	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 0.0579% East Asian · 26/44,868 alleles

Filtering AF 0.0405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0347%

Overall 0.00397% 64/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0579%	1,726
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)	0.00263%	38,063
Admixed American	0.00167%	60,006
African / African-American	0.00133%	75,038
South Asian	0.0011%	91,068

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.Arg13Gln
Coding: c.38G>A
MANE Select: NM_001003787
dbSNP: rs528919447
Type: single nucleotide variant
Location: chr17:63726694 (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.Arg13Leu Uncertain significance ★★ ⚠ same residue
STRADA p.Arg13Trp 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-arg13gln (accessed [today's date]).

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