Is OPTN p.Lys55fs (c.158_161dup) pathogenic?

OPTN p.Lys55fs (c.158161dup) is classified Pathogenic in OPTN (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-16). No gnomAD frequency available for this variant; Associated with OPTN-related open angle glaucoma.

What condition is associated with OPTN p.Lys55fs (c.158_161dup)?

OPTN p.Lys55fs (c.158_161dup) is associated with OPTN-related open angle glaucoma, amyotrophic lateral sclerosis type 12 (ClinVar).

How common is OPTN p.Lys55fs (c.158_161dup) in the general population?

OPTN p.Lys55fs (c.158_161dup) is no gnomAD frequency available for this variant (gnomAD).

OPTN p.Lys55fs

c.158_161dup · rs1564354968 · VCV576203

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

OPTN-related open angle glaucoma

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 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, 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: OPTN
Protein: p.Lys55fs
Coding: c.158_161dup
MANE Select: NM_001008212
dbSNP: rs1564354968
Type: Duplication
Location: chr10:13109279 (GRCh38)
Gene constraint: LOEUF 0.877 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.90 · 14 PDB
Residue 55: an α-helix

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

Disease context

Also linked: amyotrophic lateral sclerosis type 12

Similar variants

OPTN p.Ala436fs Pathogenic/Likely pathogenic ★★ same condition
OPTN p.Asn401fs Pathogenic ★ same condition
OPTN p.Asp445fs Pathogenic ★ same condition
OPTN p.Gln151fs Pathogenic ★ same condition
OPTN p.Glu293fs Likely pathogenic ★ same condition
OPTN p.Arg520fs Uncertain significance ★ same condition
OPTN c.1402-11dup Benign ★ same condition
OPTN c.1149-2A>G 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/optn-p-lys55fs (accessed [today's date]).

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