Is USH2A p.Arg4480= (c.13440G>A) pathogenic?

USH2A p.Arg4480= (c.13440G>A) is classified Benign/Likely benign in USH2A (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-01). Rare (popmax 0.886%, nfe); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Arg4480= (c.13440G>A)?

USH2A p.Arg4480= (c.13440G>A) is associated with Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Arg4480= (c.13440G>A) in the general population?

USH2A p.Arg4480= (c.13440G>A) is rare (popmax 0.886%, nfe) (gnomAD).

USH2A p.Arg4480=

c.13440G>A · rs111033378 · VCV48419

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.886%, nfe)

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 -0.35	GERP -3.3
Overall
CADD	1.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.886% European (non-Finnish) · 10,453/1,180,020 alleles

Filtering AF 0.872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.866%

Overall 0.705% 11,384/1,614,158 alleles · rare exomes 10,660/1,461,874 · genomes 724/152,284 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.886%	113
Remaining individualsnot grpmax-eligible	0.586%	171
Admixed American	0.283%	353
Middle Eastern	0.264%	379
Finnishnot grpmax-eligible	0.198%	504
South Asian	0.164%	611
African / African-American	0.128%	782
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229

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.Arg4480=
Coding: c.13440G>A
MANE Select: NM_206933
dbSNP: rs111033378
Type: single nucleotide variant
Location: chr1:215674471 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4480: 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

Also linked: retinitis pigmentosa 39

Similar variants

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
USH2A p.Asn346His Pathogenic ★★★ same condition
USH2A p.Asn4292Asp 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-arg4480 (accessed [today's date]).

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