Is ADGRB2 p.Pro175= (c.525C>T) pathogenic?

ADGRB2 p.Pro175= (c.525C>T) is classified Benign in ADGRB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Common (popmax 32.2%, sas) — too common for a highly-penetrant pathogenic allele.

ADGRB2 p.Pro175=

Q: How common is ADGRB2 p.Pro175= (c.525C>T) in the general population?

ADGRB2 p.Pro175= (c.525C>T) is common (popmax 32.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.525C>T · rs4949223 · VCV1600221

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 32.2%, sas) — too common for a highly-penetrant pathogenic allele

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 -1.6	GERP -3.9
Overall
CADD	3.492	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.2% South Asian · 29,308/91,088 alleles

Filtering AF 31.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.7%

Overall 13.9% 224,706/1,612,924 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	32.2%	3
Admixed American	18.9%	5
Finnishnot grpmax-eligible	17.5%	6
Remaining individualsnot grpmax-eligible	13.5%	7
Ashkenazi Jewishnot grpmax-eligible	13.1%	8
European (non-Finnish)	12.9%	8
East Asian	11.8%	8
Middle Eastern	10.6%	9
African / African-American	4.02%	25
Amishnot grpmax-eligible	2.41%	41

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.Pro175=
Coding: c.525C>T
MANE Select: NM_001364857
dbSNP: rs4949223
Type: single nucleotide variant
Location: chr1:31756312 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.10 · 1 PDB

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

Similar variants

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
ADGRB2 p.Arg1105Cys 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-pro175 (accessed [today's date]).

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