Is OPTN p.Ser308= (c.924T>G) pathogenic?

OPTN p.Ser308= (c.924T>G) is classified Likely benign in OPTN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). Ultra-rare (popmax 0.0242%, sas); Associated with Glaucoma 1, open angle, E.

What condition is associated with OPTN p.Ser308= (c.924T>G)?

OPTN p.Ser308= (c.924T>G) is associated with Glaucoma 1, open angle, E, amyotrophic lateral sclerosis type 12, OPTN-related open angle glaucoma (ClinVar).

How common is OPTN p.Ser308= (c.924T>G) in the general population?

OPTN p.Ser308= (c.924T>G) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

OPTN p.Ser308=

c.924T>G · rs779638416 · VCV1926495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Conditions

Glaucoma 1, open angle, E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -5.8
Overall
CADD	5.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0242% South Asian · 22/91,066 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00143% 23/1,613,860 alleles · ultra-rare exomes 22/1,461,646 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,139
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Ser308=
Coding: c.924T>G
MANE Select: NM_001008212
dbSNP: rs779638416
Type: single nucleotide variant
Location: chr10:13124036 (GRCh38)
Gene constraint: LOEUF 0.877 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.90 · 14 PDB
Residue 308: a UniProt-annotated variant site (in)

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

Disease context

Glaucoma 1, open angle, E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 12 OPTN-related open angle glaucoma

Similar variants

OPTN c.1149-2A>G Likely pathogenic ★★ same condition
OPTN c.626+1G>A Likely pathogenic ★★ same condition
OPTN c.780-2A>C Likely pathogenic ★★ same condition
OPTN p.Gln165Ter Pathogenic/Likely pathogenic ★★ same condition
OPTN p.Gln335Ter Pathogenic ★★ same condition
OPTN p.Gln79Ter Pathogenic/Likely pathogenic ★★ same condition
OPTN p.Glu135Ter Pathogenic ★★ same condition
OPTN p.Glu399Ter Pathogenic/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-ser308 (accessed [today's date]).

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