Is ADGRG1 p.Val412= (c.1236C>T) pathogenic?

ADGRG1 p.Val412= (c.1236C>T) is classified Benign/Likely benign in ADGRG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-16). Ultra-rare (popmax 0.0383%, amr); Associated with bilateral frontoparietal polymicrogyria.

What condition is associated with ADGRG1 p.Val412= (c.1236C>T)?

ADGRG1 p.Val412= (c.1236C>T) is associated with bilateral frontoparietal polymicrogyria (ClinVar).

How common is ADGRG1 p.Val412= (c.1236C>T) in the general population?

ADGRG1 p.Val412= (c.1236C>T) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

ADGRG1 p.Val412=

c.1236C>T · rs768769972 · VCV721086

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Conditions

bilateral frontoparietal polymicrogyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -1.9, phastCons 0.27
Overall
CADD	9.485	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0383% Admixed American · 23/60,018 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00366% 59/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,609
Remaining individualsnot grpmax-eligible	0.008%	12,497
East Asian	0.00446%	22,441
European (non-Finnish)	0.00246%	40,689

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: ADGRG1
Protein: p.Val412=
Coding: c.1236C>T
MANE Select: NM_201525
dbSNP: rs768769972
Type: single nucleotide variant
Location: chr16:57657441 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.29 · 2 PDB
Residue 412: a UniProt-annotated variant site (in cdcbm14a); an α-helix

Full ADGRG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

bilateral frontoparietal polymicrogyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADGRG1 c.1933+1G>T Pathogenic/Likely pathogenic ★★ same condition
ADGRG1 c.488-2A>G Likely pathogenic ★★ same condition
ADGRG1 c.620+1G>A Pathogenic/Likely pathogenic ★★ same condition
ADGRG1 p.Arg271Ter Pathogenic ★★ same condition
ADGRG1 p.Arg38Gln Pathogenic/Likely pathogenic ★★ same condition
ADGRG1 p.Arg470Ter Pathogenic ★★ same condition
ADGRG1 p.Arg496Ter Pathogenic ★★ same condition
ADGRG1 p.Arg559Trp Pathogenic/Likely 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/adgrg1-p-val412 (accessed [today's date]).

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