Is ADGRV1 p.Pro4483Arg (c.13448C>G) pathogenic?

ADGRV1 p.Pro4483Arg (c.13448C>G) is classified Conflicting classifications of pathogenicity in ADGRV1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-05). AlphaMissense: likely benign (0.1189); Ultra-rare (popmax 0.0214%, afr); Associated with Inborn genetic diseases.

What condition is associated with ADGRV1 p.Pro4483Arg (c.13448C>G)?

ADGRV1 p.Pro4483Arg (c.13448C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ADGRV1 p.Pro4483Arg (c.13448C>G) in the general population?

ADGRV1 p.Pro4483Arg (c.13448C>G) is ultra-rare (popmax 0.0214%, afr) (gnomAD).

What do computational predictors say about ADGRV1 p.Pro4483Arg (c.13448C>G)?

AlphaMissense predicts likely benign (score 0.1189) — an in-silico prediction, not a clinical call.

ADGRV1 p.Pro4483Arg

c.13448C>G · rs534449869 · VCV962734

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1189 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1189	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 132 kb · p 0.0071 · regional, not allelic
Overall
CADD	18.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% African / African-American · 16/74,904 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.000996% 16/1,606,288 alleles · ultra-rare exomes 4/1,454,044 · genomes 12/152,244 · joint denominator

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.Pro4483Arg
Coding: c.13448C>G
MANE Select: NM_032119
dbSNP: rs534449869
Type: single nucleotide variant
Location: chr5:90783852 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Residue 4483: the calx-beta 30 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.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
ADGRV1 p.Arg1758Ser 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-pro4483arg (accessed [today's date]).

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