Is EMX2 p.Pro87Leu (c.260C>T) pathogenic?

EMX2 p.Pro87Leu (c.260C>T) is classified Uncertain significance in EMX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-02). AlphaMissense: likely benign (0.1962); Very rare (popmax 0.00134%, afr); Associated with schizencephaly.

What condition is associated with EMX2 p.Pro87Leu (c.260C>T)?

EMX2 p.Pro87Leu (c.260C>T) is associated with schizencephaly (ClinVar).

How common is EMX2 p.Pro87Leu (c.260C>T) in the general population?

EMX2 p.Pro87Leu (c.260C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Schizencephaly inherited?

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

What do computational predictors say about EMX2 p.Pro87Leu (c.260C>T)?

AlphaMissense predicts likely benign (score 0.1962) — an in-silico prediction, not a clinical call.

EMX2 p.Pro87Leu

c.260C>T · rs754788682 · VCV1342532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

schizencephaly

Computational evidence

Protein change
AlphaMissense	0.1962	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.8, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,389 bp · p 0.33 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,642 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,458,578 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,642
European (non-Finnish)	0.00017%	589,324

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: EMX2
Protein: p.Pro87Leu
Coding: c.260C>T
MANE Select: NM_004098
dbSNP: rs754788682
Type: single nucleotide variant
Location: chr10:117543527 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.98 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 67.26

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

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EMX2 p.Gly136Val Pathogenic ⚠ same condition
EMX2 p.Ala58_Ala59dup Uncertain significance ★★ same condition
EMX2 p.Ala58_Ala59del Benign/Likely benign ★★ same condition
EMX2 p.Ser192fs Pathogenic same condition
EMX2 p.Ser192Thr Uncertain significance ★★ ⚠ same type
EMX2 c.591+6T>C Benign/Likely benign ★★ same type

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-pro87leu (accessed [today's date]).

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