Is ADGRB2 p.Val366= (c.1098G>T) pathogenic?

ADGRB2 p.Val366= (c.1098G>T) is classified Likely benign in ADGRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Very rare (popmax 0.000713%, nfe).

How common is ADGRB2 p.Val366= (c.1098G>T) in the general population?

ADGRB2 p.Val366= (c.1098G>T) is very rare (popmax 0.000713%, nfe) (gnomAD).

ADGRB2 p.Val366=

c.1098G>T · VCV3661029

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000713%, nfe)

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 5.8	GERP -3.2, phastCons 1
Overall
CADD	13.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000713% European (non-Finnish) · 8/1,122,520 alleles

Filtering AF 0.000307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000222%

Overall 0.000532% 8/1,504,334 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: ADGRB2
Protein: p.Val366=
Coding: c.1098G>T
MANE Select: NM_001364857
Type: single nucleotide variant
Location: chr1:31742992 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.10 · 1 PDB
Residue 366: the tsp type-1 2 domain

Full ADGRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRB2 p.Val366Met Uncertain significance ★ ⚠ same residue
ADGRB2 p.Ala117Val Uncertain significance ★★ ⚠ same type
ADGRB2 p.Ala1193Thr Uncertain significance ★★ ⚠ same type
ADGRB2 p.Ala1193Val Uncertain significance ★★ ⚠ same type
ADGRB2 p.Ala1411Val Uncertain significance ★★ ⚠ same type
ADGRB2 p.Ala36Thr Uncertain significance ★★ ⚠ same type
ADGRB2 p.Ala733Thr Uncertain significance ★★ ⚠ same type
ADGRB2 p.Ala901Thr Uncertain significance ★★ ⚠ 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/adgrb2-p-val366 (accessed [today's date]).

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