Is ADGRL2 p.Arg96Ser (c.288G>T) pathogenic?

ADGRL2 p.Arg96Ser (c.288G>T) is classified Uncertain significance in ADGRL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1.

How common is ADGRL2 p.Arg96Ser (c.288G>T) in the general population?

ADGRL2 p.Arg96Ser (c.288G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRL2 p.Arg96Ser (c.288G>T)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

ADGRL2 p.Arg96Ser

c.288G>T · rs747123560 · VCV2297309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,546,012)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -12.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 5.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 113 kb · p 7.5e-10 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,546,012). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADGRL2
Protein: p.Arg96Ser
Coding: c.288G>T
MANE Select: NM_001366006
dbSNP: rs747123560
Type: single nucleotide variant
Location: chr1:81936728 (GRCh38)
Gene constraint: LOEUF 0.301 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.66 · 1 PDB
Residue 96: the suel-type lectin 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-arg96ser (accessed [today's date]).

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