Is ADGRA3 p.Phe552= (c.1656C>T) pathogenic?

ADGRA3 p.Phe552= (c.1656C>T) is classified Likely benign in ADGRA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). Rare (popmax 0.109%, eas); Associated with inherited retinal dystrophy.

What condition is associated with ADGRA3 p.Phe552= (c.1656C>T)?

ADGRA3 p.Phe552= (c.1656C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ADGRA3 p.Phe552= (c.1656C>T) in the general population?

ADGRA3 p.Phe552= (c.1656C>T) is rare (popmax 0.109%, eas) (gnomAD).

ADGRA3 p.Phe552=

c.1656C>T · rs56925675 · VCV1533993

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, 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 5.8	GERP 0.22, phastCons 1
Overall
CADD	8.269	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% East Asian · 49/44,876 alleles

Filtering AF 0.0848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.00304% 49/1,614,022 alleles · rare

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.Phe552=
Coding: c.1656C>T
MANE Select: NM_145290
dbSNP: rs56925675
Type: single nucleotide variant
Location: chr4:22421039 (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.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-phe552 (accessed [today's date]).

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