Is ADGRL2 p.Arg1127= (c.3381A>G) pathogenic?

ADGRL2 p.Arg1127= (c.3381A>G) is classified Benign in ADGRL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-13). Common (popmax 6.22%, sas) — too common for a highly-penetrant pathogenic allele; Associated with ADGRL2-related disorder.

What condition is associated with ADGRL2 p.Arg1127= (c.3381A>G)?

ADGRL2 p.Arg1127= (c.3381A>G) is associated with ADGRL2-related disorder (ClinVar).

ADGRL2 p.Arg1127=

Q: How common is ADGRL2 p.Arg1127= (c.3381A>G) in the general population?

ADGRL2 p.Arg1127= (c.3381A>G) is common (popmax 6.22%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3381A>G · rs41292982 · VCV3056444

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.22%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

ADGRL2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -4.9, phastCons 0.85
Overall
CADD	5.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22% South Asian · 5,660/91,036 alleles

Filtering AF 6.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.03%

Overall 2.33% 37,605/1,612,892 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	6.22%	16
Ashkenazi Jewishnot grpmax-eligible	5.92%	17
Remaining individualsnot grpmax-eligible	2.34%	43
European (non-Finnish)	2.29%	44
Finnishnot grpmax-eligible	1.23%	81
Admixed American	0.998%	100
Middle Eastern	0.926%	108
Amishnot grpmax-eligible	0.877%	114
African / African-American	0.348%	287
East Asian	0.029%	3,449

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: ADGRL2
Protein: p.Arg1127=
Coding: c.3381A>G
MANE Select: NM_001366006
dbSNP: rs41292982
Type: single nucleotide variant
Location: chr1:81984681 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.66 · 1 PDB

Full ADGRL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ADGRL2-related disorder

Similar variants

ADGRL2 c.2734-4G>A Likely benign same condition
ADGRL2 c.3637+309A>G Benign same condition
ADGRL2 c.-9G>A Likely benign same condition
ADGRL2 p.Ala1369= Likely benign same condition
ADGRL2 p.Arg1389Lys Benign same condition
ADGRL2 p.Arg747Leu Likely benign same condition
ADGRL2 p.Asn1202Ser Benign same condition
ADGRL2 p.Asn1242= Likely benign same condition

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/adgrl2-p-arg1127 (accessed [today's date]).

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