| Gene (HGNC symbol) | Inheritance | Variant class / region | Example variants (HGVS / legacy protein) | Notable genotype-phenotype notes | Population / consanguinity / founder info | Key counts / classification | Evidence type | Key sources |
|---|---|---|---|---|---|---|---|---|
| **ADGRG1** (formerly **GPR56**) | Autosomal recessive | Disease-causing variants in classic BFPP are typically **biallelic**, often **homozygous** | Historical protein-level examples span extracellular and 7TM regions | In the landmark genotype-phenotype study, **homozygous GPR56 mutations were identified in all 29 patients with typical BFPP**; BFPP is therefore a canonical recessive ADGRG1-related cortical malformation (pqac-00000001, pqac-00000008, pqac-00000011) | Consanguinity is common in reported families, but homozygous variants were also seen in some apparently nonconsanguineous pedigrees (pqac-00000048, pqac-00000050) | OMIM BFPP 606854; ADGRG1 linked to BFPP/polymicrogyria across human cohorts (pqac-00000011, pqac-00000000) | Human clinical / human genetics | (pqac-00000001, pqac-00000008, pqac-00000011, pqac-00000048, pqac-00000050) |
| **ADGRG1** | Autosomal recessive | **Extracellular-region missense cluster**: N-terminal ECD, GPS motif, extracellular loops of 7TM | **p.Arg38Gln (R38Q), p.Arg38Trp (R38W), p.Tyr88Cys (Y88C), p.Cys91Ser (C91S), p.Cys346Ser (C346S), p.Trp349Ser (W349S), p.Arg565Trp (R565W), p.Leu640Arg (L640R)** | BFPP-associated missense variants cluster in extracellular regions and act through multiple loss-of-function mechanisms including **reduced surface expression, ER retention, defective glycosylation, impaired GPS proteolysis, altered receptor shedding, loss of ligand interaction, and altered lipid-raft distribution** (pqac-00000026, pqac-00000027, pqac-00000029, pqac-00000030, pqac-00000033) | Families reported across Arabic-speaking Middle Eastern, Pakistani, Indian, Afghani, Canadian, Turkish, Italian, Israeli, and Hispanic American backgrounds; several alleles appear recurrent/founder-like in specific pedigrees (pqac-00000050) | Missense variants were absent from 260 control chromosomes in the 2005 cohort (pqac-00000050) | Human clinical + in vitro functional | (pqac-00000026, pqac-00000027, pqac-00000029, pqac-00000030, pqac-00000033, pqac-00000050) |
| **ADGRG1** | Autosomal recessive | **Truncating variants** (nonsense / frameshift / deletion) | Historical **7-bp deletion**; nonsense and frameshift alleles noted across BFPP pedigrees | Truncating alleles are associated with severe disease and are common among the most motor-impaired/non-ambulatory cases; loss of function is an established disease mechanism (pqac-00000003, pqac-00000004, pqac-00000049) | Many truncating-variant families arise in consanguineous settings, though compound heterozygosity is also reported in the wider ADGRG1 literature (pqac-00000004, pqac-00000049) | By 2021, **77 patients from 47 pedigrees with 34 distinct ADGRG1 variants** had been reported (pqac-00000002, pqac-00000049) | Human clinical / literature review | (pqac-00000002, pqac-00000003, pqac-00000004, pqac-00000049) |
| **ADGRG1** | Autosomal recessive | **Nonsense variant in 7TM domain** | **NM_001145771.2:c.1504C>T; NP_005673.3:p.Arg502Ter / p.Arg502\***; dbSNP **rs746634404** | Reported in a child with **diffuse polymicrogyria without the classic anterior-posterior gradient**, diffuse hypomyelination, pontine/cerebellar hypoplasia, profound developmental impairment, and refractory epilepsy, expanding the ADGRG1 phenotypic spectrum beyond classic BFPP (pqac-00000003, pqac-00000041, pqac-00000046) | Found homozygously in a consanguineous family; both parents were heterozygous carriers (pqac-00000041, pqac-00000045) | Very rare in gnomAD (**f = 0.0000119** in cited report); classified as **pathogenic with very strong ACMG evidence** in the case report (pqac-00000003, pqac-00000045) | Human clinical + diagnostic genetics | (pqac-00000003, pqac-00000041, pqac-00000045, pqac-00000046) |
| **ADGRG1** | Autosomal recessive | **Novel missense variant** | **NM_201525.4:c.308T>C; p.Leu103Pro** | Identified in a large Syrian consanguineous family with ADGRG1-related polymicrogyria/BFPP; affected individuals showed early developmental delay, severe cognitive/motor impairment, oculomotor findings, and often refractory seizures with intrafamilial variability (pqac-00000012, pqac-00000042, pqac-00000043) | Reported in a **consanguineous Syrian family** with five affected individuals (pqac-00000009, pqac-00000012) | **Absent from gnomAD v2.1.1** and predicted damaging; classified as pathogenic in study workflow using ACMG-based interpretation (pqac-00000012, pqac-00000042) | Human clinical / exome sequencing | (pqac-00000009, pqac-00000012, pqac-00000042, pqac-00000043) |
| **ADGRG1** | Autosomal recessive | **Recurrent pathogenic missense variant** | **c.1693C>T; p.Arg565Trp** (legacy **R565W**) | Seen in BFPP and in severe overlapping phenotypes; associated reports include Lennox-Gastaut syndrome / drug-refractory epilepsy in some families and extensive polymicrogyria with hindbrain abnormalities in others (pqac-00000005, pqac-00000006, pqac-00000024) | Previously reported in a consanguineous Bedouin family; also detected homozygously in monozygotic twins from a consanguineous family (pqac-00000005, pqac-00000023, pqac-00000024) | In the 2024 twin report, **ClinVar pathogenic** (**VCV000005831.23**) with **CADD 29.5** (pqac-00000023, pqac-00000024) | Human clinical + curated clinical variant evidence | (pqac-00000005, pqac-00000006, pqac-00000023, pqac-00000024) |
| **ADGRG1** | Autosomal recessive | Cohort-level variant spectrum | Missense, nonsense, frameshift, deletion; recurrent alleles plus private family-specific variants | The recognized phenotype is broad: classic bilateral frontoparietal PMG with white-matter and hindbrain abnormalities, but also atypical diffuse PMG, pachygyria/lissencephaly-like presentations, and variable ambulation/cognitive outcomes (pqac-00000002, pqac-00000010, pqac-00000012, pqac-00000046) | Early literature: **8 independent mutations in 22 radiologically and clinically confirmed patients from 12 families**, with **9 families showing close parental consanguinity** and families of **Middle Eastern and French Canadian** origin; broader 2005 sampling was geographically diverse (pqac-00000048, pqac-00000050) | 2005 landmark: all 29 typical BFPP cases mutation-positive; 2021 review: 77 patients / 47 pedigrees / 34 variants (pqac-00000001, pqac-00000002, pqac-00000049) | Human clinical / literature review | (pqac-00000001, pqac-00000002, pqac-00000048, pqac-00000049, pqac-00000050) |


*Table: This table summarizes the core human genetic evidence linking ADGRG1 (GPR56) to bilateral frontoparietal polymicrogyria, including inheritance, variant classes, representative alleles, and cohort-level statistics. It is useful for quickly mapping variant-level findings to phenotypic interpretation, population context, and evidence type.*