Is ADGRG1 p.Pro70fs (c.203_206dup) pathogenic?

ADGRG1 p.Pro70fs (c.203206dup) is classified Pathogenic in ADGRG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-19). Very rare (popmax 0.00267%, afr).

How common is ADGRG1 p.Pro70fs (c.203_206dup) in the general population?

ADGRG1 p.Pro70fs (c.203_206dup) is very rare (popmax 0.00267%, afr) (gnomAD).

ADGRG1 p.Pro70fs

c.203_206dup · rs1464673111 · VCV1924588

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.086	GERP 1.7
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,944 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,128 alleles · very rare

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.Pro70fs
Coding: c.203_206dup
MANE Select: NM_201525
dbSNP: rs1464673111
Type: Duplication
Location: chr16:57651336 (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 70: a disulfide bond

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

Similar variants

ADGRG1 p.Pro70= Likely benign ★ same residue
ADGRG1 p.Pro70Leu Pathogenic ⚠ same residue
ADGRG1 p.Phe71fs Pathogenic/Likely pathogenic ★★ same type
ADGRG1 p.Val316fs Pathogenic ★★ same type
ADGRG1 p.Ala169fs Likely pathogenic ★ same type
ADGRG1 p.Ala196fs Likely pathogenic ★ same type
ADGRG1 p.Asp224fs Pathogenic ★ same type
ADGRG1 p.Gln300fs Pathogenic ★ same type

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-pro70fs (accessed [today's date]).

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