Is ADGRG1 p.Arg29= (c.87G>A) pathogenic?

ADGRG1 p.Arg29= (c.87G>A) is classified Conflicting classifications of pathogenicity in ADGRG1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-22). Very rare (popmax 0.00333%, amr); Associated with bilateral frontoparietal polymicrogyria.

What condition is associated with ADGRG1 p.Arg29= (c.87G>A)?

ADGRG1 p.Arg29= (c.87G>A) is associated with bilateral frontoparietal polymicrogyria (ClinVar).

How common is ADGRG1 p.Arg29= (c.87G>A) in the general population?

ADGRG1 p.Arg29= (c.87G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

ADGRG1 p.Arg29=

c.87G>A · rs145668224 · VCV885770

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 0.00333%, amr)

Conditions

bilateral frontoparietal polymicrogyria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.88	GERP 1.6, phastCons 0.16
Overall
CADD	10.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000991% 16/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
African / African-American	0.00267%	37,449
European (non-Finnish)	0.00102%	98,334

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.Arg29=
Coding: c.87G>A
MANE Select: NM_201525
dbSNP: rs145668224
Type: single nucleotide variant
Location: chr16:57651222 (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 29: a binding site

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-arg29 (accessed [today's date]).

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