Is ADGRA3 p.Leu17Val (c.49C>G) pathogenic?

ADGRA3 p.Leu17Val (c.49C>G) is classified Uncertain significance in ADGRA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.0791); Absent from gnomAD v4.1.

How common is ADGRA3 p.Leu17Val (c.49C>G) in the general population?

ADGRA3 p.Leu17Val (c.49C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRA3 p.Leu17Val (c.49C>G)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

ADGRA3 p.Leu17Val

c.49C>G · rs1409980766 · VCV1355944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,041,430)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.64	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 3.9	GERP -0.11, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 80 kb · p 9.9e-07 · regional, not allelic
Overall
CADD	7.712	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

No allele count reported in gnomAD v4.1 (AN 1,041,430). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADGRA3
Protein: p.Leu17Val
Coding: c.49C>G
MANE Select: NM_145290
dbSNP: rs1409980766
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.Leu17= Likely benign ★ 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-leu17val (accessed [today's date]).

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