Is USH2A p.Arg3689Ter (c.11065C>T) pathogenic?

USH2A p.Arg3689Ter (c.11065C>T) is classified Pathogenic in USH2A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00017%, nfe); Associated with Usher syndrome type 2A.

What condition is associated with USH2A p.Arg3689Ter (c.11065C>T)?

USH2A p.Arg3689Ter (c.11065C>T) is associated with Usher syndrome type 2A, retinal disorder, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Arg3689Ter (c.11065C>T) in the general population?

USH2A p.Arg3689Ter (c.11065C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

USH2A p.Arg3689Ter

c.11065C>T · rs41314534 · VCV620107

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Usher syndrome type 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 57 of 72
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.93, phastCons 0.43
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,862 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,708 alleles · very 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: USH2A
Protein: p.Arg3689Ter
Coding: c.11065C>T
MANE Select: NM_206933
dbSNP: rs41314534
Type: single nucleotide variant
Location: chr1:215759826 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3689: the fibronectin type-iii 22 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: retinal disorder retinitis pigmentosa 39 retinitis pigmentosa

Similar variants

USH2A p.Arg3689Gln Uncertain significance ★★ ⚠ same residue
USH2A p.Arg3689= Likely benign ★ 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-arg3689ter (accessed [today's date]).

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