Is OPTN p.Thr49= (c.147C>T) pathogenic?

OPTN p.Thr49= (c.147C>T) is classified Benign/Likely benign in OPTN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-23). Rare (popmax 0.673%, eas); Associated with OPTN-related open angle glaucoma.

What condition is associated with OPTN p.Thr49= (c.147C>T)?

OPTN p.Thr49= (c.147C>T) is associated with OPTN-related open angle glaucoma, amyotrophic lateral sclerosis type 12 (ClinVar).

How common is OPTN p.Thr49= (c.147C>T) in the general population?

OPTN p.Thr49= (c.147C>T) is rare (popmax 0.673%, eas) (gnomAD).

OPTN p.Thr49=

c.147C>T · rs187734249 · VCV703912

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.673%, eas)

Conditions

OPTN-related open angle glaucoma

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.2	GERP -3.5
Overall
CADD	1.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.673% East Asian · 302/44,868 alleles

Filtering AF 0.611% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.586%

Overall 0.0227% 367/1,613,924 alleles · rare exomes 307/1,461,738 · genomes 60/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.673%	149
African / African-American	0.0347%	2,885
Remaining individualsnot grpmax-eligible	0.024%	4,166
South Asian	0.00439%	22,765
Admixed American	0.00333%	30,005
Finnishnot grpmax-eligible	0.00156%	63,950
European (non-Finnish)	0.00144%	69,409

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.Thr49=
Coding: c.147C>T
MANE Select: NM_001008212
dbSNP: rs187734249
Type: single nucleotide variant
Location: chr10:13109269 (GRCh38)

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

Disease context

Also linked: amyotrophic lateral sclerosis type 12

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-thr49 (accessed [today's date]).

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