Is ADGRL2 p.Val971Phe (c.2911G>T) pathogenic?

ADGRL2 p.Val971Phe (c.2911G>T) is classified Uncertain significance in ADGRL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.2952); Absent from gnomAD v4.1.

How common is ADGRL2 p.Val971Phe (c.2911G>T) in the general population?

ADGRL2 p.Val971Phe (c.2911G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRL2 p.Val971Phe (c.2911G>T)?

AlphaMissense predicts likely benign (score 0.2952) — an in-silico prediction, not a clinical call.

ADGRL2 p.Val971Phe

c.2911G>T · VCV4242367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2952	likely benign
REVEL	0.445	indeterminate
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 3.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 21 kb · p 2e-07 · regional, not allelic
Overall
CADD	25.4	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 V967F vs ClinVar V971F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADGRL2
Protein: p.Val971Phe
Coding: c.2911G>T
MANE Select: NM_001366006
Type: single nucleotide variant
Location: chr1:81970491 (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-val971phe (accessed [today's date]).

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