Is USH2A p.Arg331Ter (c.990dup) pathogenic?

USH2A p.Arg331Ter (c.990dup) is classified Pathogenic in USH2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). No gnomAD frequency available for this variant.

How common is USH2A p.Arg331Ter (c.990dup) in the general population?

USH2A p.Arg331Ter (c.990dup) is no gnomAD frequency available for this variant (gnomAD).

USH2A p.Arg331Ter

c.990dup · rs2527440139 · VCV2023200

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 6 of 72
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.28	GERP -3

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: USH2A
Protein: p.Arg331Ter
Coding: c.990dup
MANE Select: NM_206933
dbSNP: rs2527440139
Type: Duplication
Location: chr1:216325457 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 331: the laminin n-terminal domain

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

Similar variants

USH2A p.Arg331fs Pathogenic ★ same residue
USH2A p.Arg331= Likely benign ★ same residue
USH2A p.Arg1504fs Pathogenic ★★★ same type
USH2A p.Ala1214fs Pathogenic/Likely pathogenic ★★ same type
USH2A p.Ala1717fs Likely pathogenic ★★ same type
USH2A p.Ala4678fs Pathogenic ★★ same type
USH2A p.Arg1946fs Pathogenic/Likely pathogenic ★★ same type
USH2A p.Arg205fs Pathogenic/Likely pathogenic ★★ same type

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-arg331ter (accessed [today's date]).

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