Is OPTN p.Lys360fs (c.1078_1079del) pathogenic?

OPTN p.Lys360fs (c.10781079del) is classified Pathogenic/Likely pathogenic in OPTN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-04-08). Very rare (popmax 8.47e-05%, nfe); Associated with OPTN-related open angle glaucoma.

What condition is associated with OPTN p.Lys360fs (c.1078_1079del)?

OPTN p.Lys360fs (c.1078_1079del) is associated with OPTN-related open angle glaucoma, amyotrophic lateral sclerosis type 12 (ClinVar).

How common is OPTN p.Lys360fs (c.1078_1079del) in the general population?

OPTN p.Lys360fs (c.1078_1079del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

OPTN p.Lys360fs

c.1078_1079del · rs1833438306 · VCV873266

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 10 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 0.83, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 0.000124% 2/1,613,958 alleles · very rare exomes 2/1,461,818 · genomes 0/152,140 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	8.47e-05%	1,179,956

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: OPTN
Protein: p.Lys360fs
Coding: c.1078_1079del
MANE Select: NM_001008212
dbSNP: rs1833438306
Type: Deletion
Location: chr10:13125494 (GRCh38)
Gene constraint: LOEUF 0.877 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.90 · 14 PDB

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.Asn401_Asn402insTer Pathogenic/Likely pathogenic ★★ same condition
OPTN p.Thr307fs Pathogenic/Likely pathogenic ★★ same condition
OPTN c.626+5del Uncertain significance ★★ same condition
OPTN p.Arg329fs Pathogenic ★ same condition
OPTN p.Glu175fs Pathogenic ★ same condition
OPTN p.Leu430fs Pathogenic ★ same condition
OPTN p.Lys223fs Pathogenic ★ same condition
OPTN p.Lys429fs 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-lys360fs (accessed [today's date]).

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