Is ARR3 p.Lys281fs (c.843del) pathogenic?

ARR3 p.Lys281fs (c.843del) is classified Uncertain significance in ARR3 (ClinVar, Single submitter, 1 submitter). Associated with myopia 26, X-linked, female-limited.

What condition is associated with ARR3 p.Lys281fs (c.843del)?

ARR3 p.Lys281fs (c.843del) is associated with myopia 26, X-linked, female-limited (ClinVar).

ARR3 p.Lys281fs

c.843del · VCV4533229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

myopia 26, X-linked, female-limited

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 0.31, phastCons 1

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

Variant & gene context

Gene: ARR3
Protein: p.Lys281fs
Coding: c.843del
MANE Select: NM_004312
Type: Deletion
Location: chrX:70278577 (GRCh38)
Structure: AlphaFold pLDDT 87.37
Residue 281: a UniProt-annotated variant site (in myp26; uncertain significance)

Full ARR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myopia 26, X-linked, female-limited — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARR3 c.905+2del Pathogenic ★ same condition
ARR3 c.767+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARR3 p.Arg72Ter Pathogenic/Likely pathogenic ★★ same condition
ARR3 c.1076+1G>A Uncertain significance ★ same condition
ARR3 c.609+5G>C Uncertain significance ★ same condition
ARR3 p.Arg185Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
ARR3 p.Val322Asp Uncertain significance ★ ⚠ same condition
ARR3 p.Ala298Asp 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/arr3-p-lys281fs (accessed [today's date]).

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