Is USH2A p.Arg4495= (c.13485T>A) pathogenic?

USH2A p.Arg4495= (c.13485T>A) is classified Likely benign in USH2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). Very rare (popmax 0.00533%, afr); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Arg4495= (c.13485T>A)?

USH2A p.Arg4495= (c.13485T>A) is associated with Usher syndrome type 2A (ClinVar).

How common is USH2A p.Arg4495= (c.13485T>A) in the general population?

USH2A p.Arg4495= (c.13485T>A) is very rare (popmax 0.00533%, afr) (gnomAD).

USH2A p.Arg4495=

c.13485T>A · rs533727047 · VCV794363

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Conditions

Usher syndrome type 2A

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	GERP -3
Overall
CADD	0.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,028 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000558% 9/1,614,122 alleles · very rare exomes 6/1,461,878 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,757
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000339%	295,006

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.Arg4495=
Coding: c.13485T>A
MANE Select: NM_206933
dbSNP: rs533727047
Type: single nucleotide variant
Location: chr1:215674426 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4495: the fibronectin type-iii 30 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.Arg4495Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
USH2A p.Arg4495His Conflicting classifications of pathogenicity ★ ⚠ same residue
USH2A p.Arg4495Gly Uncertain significance ★ ⚠ same residue
USH2A p.Arg4495Leu 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

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-arg4495 (accessed [today's date]).

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