Is VSX2 p.Arg28fs (c.84del) pathogenic?

VSX2 p.Arg28fs (c.84del) is classified Pathogenic in VSX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). Absent from gnomAD; Associated with isolated microphthalmia 2.

What condition is associated with VSX2 p.Arg28fs (c.84del)?

VSX2 p.Arg28fs (c.84del) is associated with isolated microphthalmia 2 (ClinVar).

How common is VSX2 p.Arg28fs (c.84del) in the general population?

VSX2 p.Arg28fs (c.84del) is absent from gnomAD (gnomAD).

VSX2 p.Arg28fs

c.84del · rs2139628382 · VCV1374787

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

isolated microphthalmia 2

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 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP -0.037, phastCons 1

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: VSX2
Protein: p.Arg28fs
Coding: c.84del
MANE Select: NM_182894
dbSNP: rs2139628382
Type: Deletion
Location: chr14:74239644 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.65
Residue 28: the 'disordered' region

Full VSX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

isolated microphthalmia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VSX2 p.Arg28= Likely benign ★ same residue
VSX2 p.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
VSX2 p.Leu232fs Likely pathogenic ★★ same condition
VSX2 p.Ala139_Leu140insTer Pathogenic ★ same condition
VSX2 p.Ala71fs Pathogenic ★ same condition
VSX2 p.Arg212fs Pathogenic ★ same condition
VSX2 p.Glu7fs Pathogenic ★ same condition
VSX2 p.Gly75fs 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/vsx2-p-arg28fs (accessed [today's date]).

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