Is ADGRA3 p.Arg472Thr (c.1415G>C) pathogenic?

ADGRA3 p.Arg472Thr (c.1415G>C) is classified Uncertain significance in ADGRA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2408); Absent from gnomAD v4.1.

How common is ADGRA3 p.Arg472Thr (c.1415G>C) in the general population?

ADGRA3 p.Arg472Thr (c.1415G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRA3 p.Arg472Thr (c.1415G>C)?

AlphaMissense predicts likely benign (score 0.2408) — an in-silico prediction, not a clinical call.

ADGRA3 p.Arg472Thr

c.1415G>C · rs2109060077 · VCV1395530

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2408	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 48 kb · p 0.57 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Arg472Thr
Coding: c.1415G>C
MANE Select: NM_145290
dbSNP: rs2109060077
Type: single nucleotide variant
Location: chr4:22435339 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20

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

Similar variants

ADGRA3 p.Arg472Lys Uncertain significance ★ ⚠ same residue
ADGRA3 p.Arg472Ser 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-arg472thr (accessed [today's date]).

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