Is ADGRA3 p.Pro350= (c.1050T>G) pathogenic?

ADGRA3 p.Pro350= (c.1050T>G) is classified Benign in ADGRA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 74.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with ADGRA3 p.Pro350= (c.1050T>G)?

ADGRA3 p.Pro350= (c.1050T>G) is associated with inherited retinal dystrophy (ClinVar).

ADGRA3 p.Pro350=

Q: How common is ADGRA3 p.Pro350= (c.1050T>G) in the general population?

ADGRA3 p.Pro350= (c.1050T>G) is common (popmax 74.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1050T>G · rs6823735 · VCV1168076

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 74.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

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 -0.3	GERP -4, phastCons 0.002
Overall
CADD	7.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 74.6% European (non-Finnish) · 878,839/1,178,312 alleles

Filtering AF 74.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.4%

Overall 71.3% 1,148,691/1,610,368 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	78.4%	1
Ashkenazi Jewishnot grpmax-eligible	76.3%	1
Finnishnot grpmax-eligible	74.7%	1
European (non-Finnish)grpmax	74.6%	1
Remaining individualsnot grpmax-eligible	69.7%	1
Admixed American	69.1%	1
East Asian	66.8%	1
Middle Eastern	61.4%	2
South Asian	61.3%	2
African / African-American	33.8%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro350=
Coding: c.1050T>G
MANE Select: NM_145290
dbSNP: rs6823735
Type: single nucleotide variant
Location: chr4:22438291 (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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADGRA3 p.Pro350Arg Uncertain significance ★ ⚠ same residue
ADGRA3 p.Arg1163Gln Uncertain significance ★★ ⚠ same condition
ADGRA3 p.Arg157Gln Uncertain significance ★★ ⚠ same condition
ADGRA3 p.Arg525Trp Uncertain significance ★★ ⚠ same condition
ADGRA3 p.Gly1303Cys Uncertain significance ★★ ⚠ same condition
ADGRA3 p.Gly1303Ser Uncertain significance ★★ ⚠ same condition
ADGRA3 p.Gly57Ser Uncertain significance ★★ ⚠ same condition
ADGRA3 p.Leu798Phe Uncertain significance ★★ ⚠ same condition

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-pro350 (accessed [today's date]).

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