Is ADGRL2 p.Ala29Val (c.86C>T) pathogenic?

ADGRL2 p.Ala29Val (c.86C>T) is classified Uncertain significance in ADGRL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.7375); Very rare (popmax 0.00667%, afr).

How common is ADGRL2 p.Ala29Val (c.86C>T) in the general population?

ADGRL2 p.Ala29Val (c.86C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about ADGRL2 p.Ala29Val (c.86C>T)?

AlphaMissense predicts likely pathogenic (score 0.7375) — an in-silico prediction, not a clinical call.

ADGRL2 p.Ala29Val

c.86C>T · VCV3499805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7375 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7375	likely pathogenic
REVEL	0.551	indeterminate
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 113 kb · p 7.5e-10 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/75,008 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000411% 6/1,460,870 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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.Ala29Val
Coding: c.86C>T
MANE Select: NM_001366006
Type: single nucleotide variant
Location: chr1:81907029 (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.Ala402Thr 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-ala29val (accessed [today's date]).

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