Is STRADA p.Ser47Ter (c.140C>G) pathogenic?

STRADA p.Ser47Ter (c.140C>G) is classified Conflicting classifications of pathogenicity in STRADA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-11-18). Ultra-rare (popmax 0.015%, nfe); Associated with polyhydramnios, megalencephaly, and symptomatic epilepsy.

What condition is associated with STRADA p.Ser47Ter (c.140C>G)?

STRADA p.Ser47Ter (c.140C>G) is associated with polyhydramnios, megalencephaly, and symptomatic epilepsy (ClinVar).

How common is STRADA p.Ser47Ter (c.140C>G) in the general population?

STRADA p.Ser47Ter (c.140C>G) is ultra-rare (popmax 0.015%, nfe) (gnomAD).

STRADA p.Ser47Ter

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

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

c.140C>G · rs375396155 · VCV942810

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, nfe)

Conditions

polyhydramnios, megalencephaly, and symptomatic epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	38.0	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

Grpmax group 0.015% European (non-Finnish) · 177/1,179,508 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0113% 182/1,613,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.015%	6,664
Remaining individualsnot grpmax-eligible	0.00481%	20,809
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
African / African-American	0.00134%	74,866

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.Ser47Ter
Coding: c.140C>G
MANE Select: NM_001003787
dbSNP: rs375396155
Type: single nucleotide variant
Location: chr17:63714092 (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.Ser47= 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-ser47ter (accessed [today's date]).

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