Is USH2A p.Arg3484Ter (c.10450C>T) pathogenic?

USH2A p.Arg3484Ter (c.10450C>T) is classified Pathogenic/Likely pathogenic in USH2A (ClinVar, Multiple submitters, 12 submitters; last evaluated 2025-12-22). Very rare (popmax 0.005%, amr); Associated with USH2A-related disorder.

What condition is associated with USH2A p.Arg3484Ter (c.10450C>T)?

USH2A p.Arg3484Ter (c.10450C>T) is associated with USH2A-related disorder, Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Arg3484Ter (c.10450C>T) in the general population?

USH2A p.Arg3484Ter (c.10450C>T) is very rare (popmax 0.005%, amr) (gnomAD).

USH2A p.Arg3484Ter

c.10450C>T · rs111033379 · VCV48348

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

USH2A-related disorder

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 53 of 72
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP -1.4
Overall
CADD	38.0	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 0.005% Admixed American · 3/59,952 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00186% 30/1,613,748 alleles · very rare exomes 30/1,461,586 · genomes 0/152,162 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Finnishnot grpmax-eligible	0.00625%	16,000
Admixed Americangrpmax	0.005%	19,984
South Asian	0.00329%	30,357
African / African-American	0.00133%	74,972
European (non-Finnish)	0.0011%	90,758

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg3484Ter
Coding: c.10450C>T
MANE Select: NM_206933
dbSNP: rs111033379
Type: single nucleotide variant
Location: chr1:215782873 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3484: the fibronectin type-iii 19 domain

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

Disease context

Also linked: Usher syndrome type 2A retinitis pigmentosa 39 inherited retinal dystrophy Usher syndrome

Similar variants

USH2A p.Arg3484Gln Uncertain significance ★★ ⚠ same residue
USH2A p.Arg3484= 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-arg3484ter (accessed [today's date]).

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