Is ADGRA3 p.Leu17= (c.49C>T) pathogenic?

ADGRA3 p.Leu17= (c.49C>T) is classified Likely benign in ADGRA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). Ultra-rare (popmax 0.0185%, eas).

How common is ADGRA3 p.Leu17= (c.49C>T) in the general population?

ADGRA3 p.Leu17= (c.49C>T) is ultra-rare (popmax 0.0185%, eas) (gnomAD).

ADGRA3 p.Leu17=

c.49C>T · VCV4764670

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, eas)

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 3.9	GERP -0.11, phastCons 1
Overall
CADD	6.691	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0185% East Asian · 2/10,812 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00048% 5/1,041,430 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0185%	5,406
European (non-Finnish)	0.000344%	290,411

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: ADGRA3
Protein: p.Leu17=
Coding: c.49C>T
MANE Select: NM_145290
Type: single nucleotide variant
Location: chr4:22515736 (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.Leu17Val Uncertain significance ★ ⚠ same residue
ADGRA3 p.Leu17_Pro18insLeuLeu 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-leu17 (accessed [today's date]).

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