Is ADGRL2 p.Ser766= (c.2298C>T) pathogenic?

ADGRL2 p.Ser766= (c.2298C>T) is classified Benign in ADGRL2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-02-01). Rare (popmax 0.148%, nfe).

How common is ADGRL2 p.Ser766= (c.2298C>T) in the general population?

ADGRL2 p.Ser766= (c.2298C>T) is rare (popmax 0.148%, nfe) (gnomAD).

ADGRL2 p.Ser766=

c.2298C>T · rs150187776 · VCV2638902

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.084	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 5.3, phastCons 1
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% European (non-Finnish) · 1,745/1,179,972 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.14%

Overall 0.119% 1,926/1,613,908 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)grpmax	0.148%	676
Remaining individualsnot grpmax-eligible	0.123%	811
Admixed American	0.0883%	1,132
Finnishnot grpmax-eligible	0.0437%	2,286
African / African-American	0.0267%	3,744

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser766=
Coding: c.2298C>T
MANE Select: NM_001366006
dbSNP: rs150187776
Type: single nucleotide variant
Location: chr1:81966558 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.66 · 1 PDB
Residue 766: the gain-b domain

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

Similar variants

ADGRL2 p.Lys555Arg Likely benign ★★ same type
ADGRL2 p.Thr1294= Benign ★★ same type
ADGRL2 p.Ala1070Thr Uncertain significance ★ ⚠ same type
ADGRL2 p.Ala1090Val Uncertain significance ★ ⚠ same type
ADGRL2 p.Ala160Val Uncertain significance ★ ⚠ same type
ADGRL2 p.Ala170Val Uncertain significance ★ ⚠ same type
ADGRL2 p.Ala191Ser Uncertain significance ★ ⚠ same type
ADGRL2 p.Ala29Val 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/adgrl2-p-ser766 (accessed [today's date]).

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