Is USH2A p.Arg3491= (c.10473A>G) pathogenic?

USH2A p.Arg3491= (c.10473A>G) is classified Uncertain significance in USH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 0.00223%, eas); Associated with inherited retinal dystrophy.

What condition is associated with USH2A p.Arg3491= (c.10473A>G)?

USH2A p.Arg3491= (c.10473A>G) is associated with inherited retinal dystrophy (ClinVar).

How common is USH2A p.Arg3491= (c.10473A>G) in the general population?

USH2A p.Arg3491= (c.10473A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

USH2A p.Arg3491=

c.10473A>G · rs1661682573 · VCV3028681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1	GERP -3.2
Overall
CADD	3.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,860 alleles

Overall 6.2e-05% 1/1,613,978 alleles · very rare exomes 1/1,461,664 · genomes 0/152,314 · joint denominator

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: USH2A
Protein: p.Arg3491=
Coding: c.10473A>G
MANE Select: NM_206933
dbSNP: rs1661682573
Type: single nucleotide variant
Location: chr1:215782850 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3491: the fibronectin type-iii 19 domain

Full USH2A 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

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
USH2A p.Asn346His Pathogenic ★★★ same condition
USH2A p.Asn4292Asp Likely pathogenic ★★★ ⚠ same condition
USH2A p.Cys759Phe 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-arg3491 (accessed [today's date]).

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