Is USH2A p.Arg517= (c.1551A>G) pathogenic?

USH2A p.Arg517= (c.1551A>G) is classified Uncertain significance in USH2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-20). Absent from gnomAD v4.1; Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Arg517= (c.1551A>G)?

USH2A p.Arg517= (c.1551A>G) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Arg517= (c.1551A>G) in the general population?

USH2A p.Arg517= (c.1551A>G) is absent from gnomAD v4.1 (gnomAD).

USH2A p.Arg517=

c.1551A>G · VCV4062719

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Usher syndrome type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	acceptor loss, 25 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -2.9	GERP -3.4
Overall
CADD	6.557	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: USH2A
Protein: p.Arg517=
Coding: c.1551A>G
MANE Select: NM_206933
Type: single nucleotide variant
Location: chr1:216321976 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 517: a UniProt-annotated variant site (in ush2a; uncertain significance); the laminin n-terminal domain

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH2A p.Arg517Thr Conflicting classifications of pathogenicity ★ same residue
USH2A p.Arg517Ser Uncertain significance ★ same residue
USH2A c.12295-3T>A Pathogenic ★★★ same condition
USH2A c.8559-2A>G Pathogenic ★★★ same condition
USH2A c.8682-9A>G Pathogenic ★★★ same condition
USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same condition
USH2A p.Arg4192Cys Likely pathogenic ★★★ ⚠ 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/ush2a-p-arg517 (accessed [today's date]).

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