Is ADGRA3 p.Ala41= (c.123C>G) pathogenic?

ADGRA3 p.Ala41= (c.123C>G) is classified Likely benign in ADGRA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). Ultra-rare (popmax 0.0284%, sas).

How common is ADGRA3 p.Ala41= (c.123C>G) in the general population?

ADGRA3 p.Ala41= (c.123C>G) is ultra-rare (popmax 0.0284%, sas) (gnomAD).

ADGRA3 p.Ala41=

c.123C>G · VCV3617633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, sas)

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 -2.3	GERP -1.9
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% South Asian · 11/38,752 alleles

Filtering AF 0.0159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.00104% 13/1,253,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0284%	3,523
Finnishnot grpmax-eligible	0.00244%	40,906
African / African-American	0.00158%	63,314

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.Ala41=
Coding: c.123C>G
MANE Select: NM_145290
Type: single nucleotide variant
Location: chr4:22515662 (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.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-ala41 (accessed [today's date]).

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