Is ADGRB2 p.Pro340= (c.1020C>A) pathogenic?

ADGRB2 p.Pro340= (c.1020C>A) is classified Likely benign in ADGRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). Very rare (popmax 0.000349%, nfe).

How common is ADGRB2 p.Pro340= (c.1020C>A) in the general population?

ADGRB2 p.Pro340= (c.1020C>A) is very rare (popmax 0.000349%, nfe) (gnomAD).

ADGRB2 p.Pro340=

c.1020C>A · rs1283437918 · VCV2880798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000349%, 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 3.5	GERP -2.6, phastCons 1
Overall
CADD	9.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000349% European (non-Finnish) · 4/1,146,756 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000258% 4/1,551,168 alleles · very rare exomes 4/1,398,872 · genomes 0/152,296 · joint denominator

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.Pro340=
Coding: c.1020C>A
MANE Select: NM_001364857
dbSNP: rs1283437918
Type: single nucleotide variant
Location: chr1:31744260 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.10 · 1 PDB
Residue 340: the tsp type-1 1 domain

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

Similar variants

ADGRB2 p.Pro340Arg Uncertain significance ★ ⚠ same residue
ADGRB2 p.Pro340His Uncertain significance ★ ⚠ same residue
ADGRB2 p.Pro340Leu 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

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-pro340 (accessed [today's date]).

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