Is ADGRA3 p.Asp698Val (c.2093A>T) pathogenic?

ADGRA3 p.Asp698Val (c.2093A>T) is classified Uncertain significance in ADGRA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: ambiguous (0.3775); Absent from gnomAD v4.1.

How common is ADGRA3 p.Asp698Val (c.2093A>T) in the general population?

ADGRA3 p.Asp698Val (c.2093A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRA3 p.Asp698Val (c.2093A>T)?

AlphaMissense predicts ambiguous (score 0.3775) — an in-silico prediction, not a clinical call.

ADGRA3 p.Asp698Val

c.2093A>T · VCV3684694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3775	ambiguous
REVEL	0.572	indeterminate
SaProt	LLR -9.25	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 48 kb · p 0.57 · regional, not allelic
Overall
CADD	27.5	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.Asp698Val
Coding: c.2093A>T
MANE Select: NM_145290
Type: single nucleotide variant
Location: chr4:22413321 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 698: the gain-b domain

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

Similar variants

ADGRA3 p.Asp698His 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
ADGRA3 p.Ala37Gly 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-asp698val (accessed [today's date]).

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