Is ADGRA3 p.Thr1259= (c.3777C>G) pathogenic?

ADGRA3 p.Thr1259= (c.3777C>G) is classified Likely benign in ADGRA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). Absent from gnomAD v4.1.

How common is ADGRA3 p.Thr1259= (c.3777C>G) in the general population?

ADGRA3 p.Thr1259= (c.3777C>G) is absent from gnomAD v4.1 (gnomAD).

ADGRA3 p.Thr1259=

c.3777C>G · rs2474685592 · VCV2095121

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -5.1
Overall
CADD	0.142	PHRED · no single calibrated threshold — expert panels disagree

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.Thr1259=
Coding: c.3777C>G
MANE Select: NM_145290
dbSNP: rs2474685592
Type: single nucleotide variant
Location: chr4:22387894 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 1259: the 'disordered' region

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

Similar variants

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
ADGRA3 p.Ala407Thr 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-thr1259 (accessed [today's date]).

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