Is ADGRB2 p.Pro394Ser (c.1180C>T) pathogenic?

ADGRB2 p.Pro394Ser (c.1180C>T) is classified Uncertain significance in ADGRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: ambiguous (0.4705); Very rare (popmax 0.00248%, eas).

How common is ADGRB2 p.Pro394Ser (c.1180C>T) in the general population?

ADGRB2 p.Pro394Ser (c.1180C>T) is very rare (popmax 0.00248%, eas) (gnomAD).

What do computational predictors say about ADGRB2 p.Pro394Ser (c.1180C>T)?

AlphaMissense predicts ambiguous (score 0.4705) — an in-silico prediction, not a clinical call.

ADGRB2 p.Pro394Ser

c.1180C>T · rs1646057028 · VCV3084022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00248%, eas)

Computational evidence

Protein change
AlphaMissense	0.4705	ambiguous
REVEL	0.293	indeterminate
SaProt	LLR -7.67	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 17 kb · p 5.9e-11 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00248% East Asian · 1/40,314 alleles

Overall 6.48e-05% 1/1,542,042 alleles · very rare exomes 1/1,389,740 · genomes 0/152,302 · 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.Pro394Ser
Coding: c.1180C>T
MANE Select: NM_001364857
dbSNP: rs1646057028
Type: single nucleotide variant
Location: chr1:31742910 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.10 · 1 PDB
Residue 394: the tsp type-1 2 domain

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-pro394ser (accessed [today's date]).

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