Is EMX2 p.Ser192fs (c.575_576insA) pathogenic?

EMX2 p.Ser192fs (c.575576insA) is classified Pathogenic in EMX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1996-01-01). Absent from gnomAD; Associated with schizencephaly.

What condition is associated with EMX2 p.Ser192fs (c.575_576insA)?

EMX2 p.Ser192fs (c.575_576insA) is associated with schizencephaly (ClinVar).

How common is EMX2 p.Ser192fs (c.575_576insA) in the general population?

EMX2 p.Ser192fs (c.575_576insA) is absent from gnomAD (gnomAD).

How is Schizencephaly inherited?

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

EMX2 p.Ser192fs

c.575_576insA · rs2133969658 · VCV9519

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

schizencephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (2 of 3, 16 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMX2
Protein: p.Ser192fs
Coding: c.575_576insA
MANE Select: NM_004098
dbSNP: rs2133969658
Type: Insertion
Location: chr10:117545800 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.98 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 67.26
Residue 192: a DNA-binding region

Full EMX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

schizencephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Schizencephaly (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (United Kingdom)

Similar variants

EMX2 p.Ser192Thr Uncertain significance ★★ ⚠ same residue
EMX2 p.Ala58_Ala59dup Uncertain significance ★★ same condition
EMX2 p.Ala58_Ala59del Benign/Likely benign ★★ same condition
EMX2 p.Pro87Leu Uncertain significance ★ ⚠ same condition
EMX2 c.407-1G>A Pathogenic same condition
EMX2 c.407-4G>T Pathogenic same condition
EMX2 p.Gly136Val Pathogenic ⚠ 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/emx2-p-ser192fs (accessed [today's date]).

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