Is ADGRA3 p.Arg330Gly (c.988C>G) pathogenic?

ADGRA3 p.Arg330Gly (c.988C>G) is classified Uncertain significance in ADGRA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.8258); Absent from gnomAD v4.1.

How common is ADGRA3 p.Arg330Gly (c.988C>G) in the general population?

ADGRA3 p.Arg330Gly (c.988C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRA3 p.Arg330Gly (c.988C>G)?

AlphaMissense predicts likely pathogenic (score 0.8258) — an in-silico prediction, not a clinical call.

ADGRA3 p.Arg330Gly

c.988C>G · rs775111076 · VCV1523115

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8258 · 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	0.8258	likely pathogenic
REVEL	0.392	indeterminate
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.35	acceptor loss, 42 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 80 kb · p 9.9e-07 · regional, not allelic
Overall
CADD	32.0	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

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: ADGRA3
Protein: p.Arg330Gly
Coding: c.988C>G
MANE Select: NM_145290
dbSNP: rs775111076
Type: single nucleotide variant
Location: chr4:22438353 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 330: the ig-like domain

Full ADGRA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRA3 p.Arg330Cys Uncertain significance ★ ⚠ same residue
ADGRA3 p.Arg330His Uncertain significance ★ ⚠ same residue
ADGRA3 p.Ala1008Val Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala1120Val Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala1127Ser Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala177Val Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala26Pro Uncertain significance ★★ ⚠ same type
ADGRA3 p.Ala316Pro 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/adgra3-p-arg330gly (accessed [today's date]).

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