Is ADGRL2 p.Ser539= (c.1617C>T) pathogenic?

ADGRL2 p.Ser539= (c.1617C>T) is classified Likely benign in ADGRL2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-24). Rare (popmax 0.402%, mid); Associated with ADGRL2-related disorder.

What condition is associated with ADGRL2 p.Ser539= (c.1617C>T)?

ADGRL2 p.Ser539= (c.1617C>T) is associated with ADGRL2-related disorder (ClinVar).

How common is ADGRL2 p.Ser539= (c.1617C>T) in the general population?

ADGRL2 p.Ser539= (c.1617C>T) is rare (popmax 0.402%, mid) (gnomAD).

ADGRL2 p.Ser539=

c.1617C>T · rs201068501 · VCV3038465

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.402%, mid)

Conditions

ADGRL2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.163	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -1.8, phastCons 0.78
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.402% Middle Eastern · 24/5,966 alleles

Filtering AF 0.277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0055% 88/1,600,420 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.402%	249
Remaining individualsnot grpmax-eligible	0.0227%	4,413
South Asian	0.0135%	7,399
Admixed American	0.00859%	11,636
African / African-American	0.00269%	37,133
European (non-Finnish)	0.00264%	37,855

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.Ser539=
Coding: c.1617C>T
MANE Select: NM_001366006
dbSNP: rs201068501
Type: single nucleotide variant
Location: chr1:81951965 (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.Arg1127= Benign same condition
ADGRL2 p.Arg1389Lys Benign same condition
ADGRL2 p.Arg747Leu Likely benign same condition
ADGRL2 p.Asn1202Ser 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-ser539 (accessed [today's date]).

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