Is ADGRG1 p.Arg470Pro (c.1409G>C) pathogenic?

ADGRG1 p.Arg470Pro (c.1409G>C) is classified Uncertain significance in ADGRG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.642); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADGRG1 p.Arg470Pro (c.1409G>C)?

ADGRG1 p.Arg470Pro (c.1409G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ADGRG1 p.Arg470Pro (c.1409G>C) in the general population?

ADGRG1 p.Arg470Pro (c.1409G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRG1 p.Arg470Pro (c.1409G>C)?

AlphaMissense predicts likely pathogenic (score 0.642) — an in-silico prediction, not a clinical call.

ADGRG1 p.Arg470Pro

c.1409G>C · VCV4569613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.642	likely pathogenic
REVEL	0.15	moderately benign-leaning
SaProt	LLR -13.88	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.64, phastCons 0.006
Regional constraint	o/e 0.91	unconstrained · MANE · 13 kb · p 0.0093 · regional, not allelic
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R476P vs ClinVar R470P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADGRG1
Protein: p.Arg470Pro
Coding: c.1409G>C
MANE Select: NM_201525
Type: single nucleotide variant
Location: chr16:57659535 (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 470: a UniProt-annotated variant site (in cdcbm14a)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADGRG1 p.Arg470Gln Uncertain significance ★ ⚠ same residue
ADGRG1 p.Arg470Ter Pathogenic ★★ same residue
ADGRG1 p.Arg470Gly Uncertain significance ★ ⚠ same residue
ADGRG1 p.Ala625Val Uncertain significance ★★ ⚠ same condition
ADGRG1 p.Ala673Thr Uncertain significance ★★ ⚠ same condition
ADGRG1 p.Arg108Cys Uncertain significance ★★ ⚠ same condition
ADGRG1 p.Arg232Gln Uncertain significance ★★ ⚠ same condition
ADGRG1 p.Arg33His Uncertain significance ★★ ⚠ 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-arg470pro (accessed [today's date]).

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