Is OPTN p.Cys472Arg (c.1414T>C) pathogenic?

OPTN p.Cys472Arg (c.1414T>C) is classified Uncertain significance in OPTN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-30). AlphaMissense: likely pathogenic (0.6699); Absent from gnomAD v4.1; Associated with OPTN-related open angle glaucoma.

What condition is associated with OPTN p.Cys472Arg (c.1414T>C)?

OPTN p.Cys472Arg (c.1414T>C) is associated with OPTN-related open angle glaucoma (ClinVar).

How common is OPTN p.Cys472Arg (c.1414T>C) in the general population?

OPTN p.Cys472Arg (c.1414T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPTN p.Cys472Arg (c.1414T>C)?

AlphaMissense predicts likely pathogenic (score 0.6699) — an in-silico prediction, not a clinical call.

OPTN p.Cys472Arg

c.1414T>C · rs1833604353 · VCV932115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6699 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

OPTN-related open angle glaucoma

Computational evidence

Protein change
AlphaMissense	0.6699	likely pathogenic
REVEL	0.504	indeterminate
SaProt	LLR -5.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 28 kb · p 0.058 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OPTN
Protein: p.Cys472Arg
Coding: c.1414T>C
MANE Select: NM_001008212
dbSNP: rs1833604353
Type: single nucleotide variant
Location: chr10:13132079 (GRCh38)
Gene constraint: LOEUF 0.877 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.90 · 14 PDB
Residue 472: an α-helix; the 'interaction with hd' region; the 'interaction with myo6' region

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

Disease context

OPTN-related open angle glaucoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-cys472arg (accessed [today's date]).

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