Is STRADA p.Ile11Ser (c.32T>G) pathogenic?

STRADA p.Ile11Ser (c.32T>G) is classified Uncertain significance in STRADA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-02). AlphaMissense: likely pathogenic (0.6285); Ultra-rare (popmax 0.0714%, eas); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Ile11Ser (c.32T>G)?

STRADA p.Ile11Ser (c.32T>G) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Ile11Ser (c.32T>G) in the general population?

STRADA p.Ile11Ser (c.32T>G) is ultra-rare (popmax 0.0714%, eas) (gnomAD).

What do computational predictors say about STRADA p.Ile11Ser (c.32T>G)?

AlphaMissense predicts likely pathogenic (score 0.6285) — an in-silico prediction, not a clinical call.

STRADA p.Ile11Ser

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

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

c.32T>G · rs377651050 · VCV536757

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6285 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
AlphaMissense	0.6285	likely pathogenic
REVEL	0.272	benign-leaning
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0714% East Asian · 32/44,842 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0453%

Overall 0.00397% 64/1,613,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0714%	1,401
Remaining individualsnot grpmax-eligible	0.0448%	2,231
African / African-American	0.00401%	24,967
Admixed American	0.00167%	59,946

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.Ile11Ser
Coding: c.32T>G
MANE Select: NM_001003787
dbSNP: rs377651050
Type: single nucleotide variant
Location: chr17:63728338 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.46 · 4 PDB

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.Ile11= 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
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-ile11ser (accessed [today's date]).

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