Is ADGRG1 p.Pro200Ser (c.598C>T) pathogenic?

ADGRG1 p.Pro200Ser (c.598C>T) is classified Uncertain significance in ADGRG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). AlphaMissense: likely benign (0.078); Very rare (popmax 0.00267%, afr).

How common is ADGRG1 p.Pro200Ser (c.598C>T) in the general population?

ADGRG1 p.Pro200Ser (c.598C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ADGRG1 p.Pro200Ser (c.598C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

ADGRG1 p.Pro200Ser

c.598C>T · rs758907377 · VCV2176905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.26, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 13 kb · p 0.0093 · regional, not allelic
Overall
CADD	15.38	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,034 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000754% 11/1,458,140 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,517
European (non-Finnish)	0.000763%	131,097

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.Pro200Ser
Coding: c.598C>T
MANE Select: NM_201525
dbSNP: rs758907377
Type: single nucleotide variant
Location: chr16:57653313 (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 200: a binding site

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

Similar variants

ADGRG1 p.Pro200= Likely benign ★ same residue
ADGRG1 c.1933+1G>T Pathogenic/Likely pathogenic ★★ same type
ADGRG1 c.488-2A>G Likely pathogenic ★★ same type
ADGRG1 c.620+1G>A Pathogenic/Likely pathogenic ★★ same type
ADGRG1 p.Arg271Ter Pathogenic ★★ same type
ADGRG1 p.Arg38Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
ADGRG1 p.Arg470Ter Pathogenic ★★ same type
ADGRG1 p.Arg496Ter 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-pro200ser (accessed [today's date]).

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