Is ADGRA3 p.Leu671= (c.2013C>T) pathogenic?

ADGRA3 p.Leu671= (c.2013C>T) is classified Benign in ADGRA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 4.39%, eas); Associated with inherited retinal dystrophy.

What condition is associated with ADGRA3 p.Leu671= (c.2013C>T)?

ADGRA3 p.Leu671= (c.2013C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ADGRA3 p.Leu671= (c.2013C>T) in the general population?

ADGRA3 p.Leu671= (c.2013C>T) is low-frequency (popmax 4.39%, eas) (gnomAD).

ADGRA3 p.Leu671=

c.2013C>T · rs113497728 · VCV790829

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.39%, eas)

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 3.9	GERP 0.45, phastCons 1
Overall
CADD	8.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.39% East Asian · 1,968/44,842 alleles

Filtering AF 4.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.16%

Overall 0.428% 6,899/1,613,542 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.39%	23
Finnishnot grpmax-eligible	2.5%	40
South Asian	2.17%	46
Remaining individualsnot grpmax-eligible	0.731%	137
African / African-American	0.541%	185
Middle Eastern	0.198%	505
Admixed American	0.0567%	1,765
European (non-Finnish)	0.0381%	2,627

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.Leu671=
Coding: c.2013C>T
MANE Select: NM_145290
dbSNP: rs113497728
Type: single nucleotide variant
Location: chr4:22413611 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.20
Residue 671: the gain-b domain

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.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
ADGRA3 p.Met1147Thr 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-leu671 (accessed [today's date]).

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