Is ADGRL2 p.Ala1230Pro (c.3688G>C) pathogenic?

ADGRL2 p.Ala1230Pro (c.3688G>C) is classified Likely benign in ADGRL2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.3157); Rare (popmax 0.881%, nfe).

How common is ADGRL2 p.Ala1230Pro (c.3688G>C) in the general population?

ADGRL2 p.Ala1230Pro (c.3688G>C) is rare (popmax 0.881%, nfe) (gnomAD).

What do computational predictors say about ADGRL2 p.Ala1230Pro (c.3688G>C)?

AlphaMissense predicts likely benign (score 0.3157) — an in-silico prediction, not a clinical call.

ADGRL2 p.Ala1230Pro

c.3688G>C · rs72719419 · VCV3042178

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3157 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.881%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3157	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,119 bp · p 0.34 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1220P vs ClinVar A1230P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.881% European (non-Finnish) · 10,399/1,179,910 alleles

Filtering AF 0.867% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.861%

Overall 0.694% 11,207/1,613,964 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.881%	113
Remaining individualsnot grpmax-eligible	0.488%	205
Admixed American	0.352%	284
African / African-American	0.159%	630
South Asian	0.102%	979
Finnishnot grpmax-eligible	0.0969%	1,032
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,849
Middle Eastern	0.033%	3,027

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.Ala1230Pro
Coding: c.3688G>C
MANE Select: NM_001366006
dbSNP: rs72719419
Type: single nucleotide variant
Location: chr1:81990423 (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

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-ala1230pro (accessed [today's date]).

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