Is ADGRV1 p.Ala2829Pro (c.8485G>C) pathogenic?

ADGRV1 p.Ala2829Pro (c.8485G>C) is classified Uncertain significance in ADGRV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely pathogenic (0.5738); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADGRV1 p.Ala2829Pro (c.8485G>C)?

ADGRV1 p.Ala2829Pro (c.8485G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ADGRV1 p.Ala2829Pro (c.8485G>C) in the general population?

ADGRV1 p.Ala2829Pro (c.8485G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ADGRV1 p.Ala2829Pro (c.8485G>C)?

AlphaMissense predicts likely pathogenic (score 0.5738) — an in-silico prediction, not a clinical call.

ADGRV1 p.Ala2829Pro

c.8485G>C · rs2531081217 · VCV2536673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5738	likely pathogenic
REVEL	0.762	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 132 kb · p 0.0071 · regional, not allelic
Overall
CADD	24.8	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,800 alleles

Overall 6.84e-05% 1/1,461,594 alleles · very rare

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: ADGRV1
Protein: p.Ala2829Pro
Coding: c.8485G>C
MANE Select: NM_032119
dbSNP: rs2531081217
Type: single nucleotide variant
Location: chr5:90705498 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Residue 2829: the calx-beta 20 domain

Full ADGRV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADGRV1 p.Ala2829Val Uncertain significance ★ same residue
ADGRV1 p.Ala1630Val Uncertain significance ★★ ⚠ same condition
ADGRV1 p.Ala3019Val Uncertain significance ★★ ⚠ same condition
ADGRV1 p.Ala3314Thr Uncertain significance ★★ ⚠ same condition
ADGRV1 p.Ala3945Thr Uncertain significance ★★ same condition
ADGRV1 p.Ala4645Thr Uncertain significance ★★ ⚠ same condition
ADGRV1 p.Ala5208Thr Uncertain significance ★★ ⚠ same condition
ADGRV1 p.Ala5212Thr Uncertain significance ★★ ⚠ same condition

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/adgrv1-p-ala2829pro (accessed [today's date]).

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