Is ADGRG1 p.Ser61= (c.183C>T) pathogenic?

ADGRG1 p.Ser61= (c.183C>T) is classified Conflicting classifications of pathogenicity in ADGRG1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-11). Very rare (popmax 0.00891%, eas); Associated with bilateral frontoparietal polymicrogyria.

What condition is associated with ADGRG1 p.Ser61= (c.183C>T)?

ADGRG1 p.Ser61= (c.183C>T) is associated with bilateral frontoparietal polymicrogyria (ClinVar).

How common is ADGRG1 p.Ser61= (c.183C>T) in the general population?

ADGRG1 p.Ser61= (c.183C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

ADGRG1 p.Ser61=

c.183C>T · rs200846541 · VCV885771

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 -20	GERP -3.4
Overall
CADD	2.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,872 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000805% 13/1,614,174 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,930
East Asiangrpmax	0.00891%	11,218
South Asian	0.0022%	45,539

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser61=
Coding: c.183C>T
MANE Select: NM_201525
dbSNP: rs200846541
Type: single nucleotide variant
Location: chr16:57651318 (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 61: a disulfide bond

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-ser61 (accessed [today's date]).

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