Is OPTN p.Thr34= (c.102G>A) pathogenic?

OPTN p.Thr34= (c.102G>A) is classified Benign in OPTN (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 29.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with OPTN-related open angle glaucoma.

What condition is associated with OPTN p.Thr34= (c.102G>A)?

OPTN p.Thr34= (c.102G>A) is associated with OPTN-related open angle glaucoma, amyotrophic lateral sclerosis type 12 (ClinVar).

OPTN p.Thr34=

Q: How common is OPTN p.Thr34= (c.102G>A) in the general population?

OPTN p.Thr34= (c.102G>A) is common (popmax 29.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.102G>A · rs2234968 · VCV96022

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 29.7%, mid) — too common for a highly-penetrant pathogenic allele

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 -9.9	GERP -3.3
Overall
CADD	0.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29.7% Middle Eastern · 1,801/6,060 alleles

Filtering AF 28.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.1%

Overall 25.1% 404,990/1,613,578 alleles · common exomes 374,781/1,461,578 · genomes 30,209/152,000 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	32.8%	3
Middle Easterngrpmax	29.7%	3
Admixed American	27.2%	4
European (non-Finnish)	26.9%	4
Remaining individualsnot grpmax-eligible	25%	4
South Asian	22.2%	5
East Asian	18.7%	5
Finnishnot grpmax-eligible	18.6%	5
Amishnot grpmax-eligible	10.5%	10
African / African-American	4.93%	20

Ashkenazi Jewish 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.Thr34=
Coding: c.102G>A
MANE Select: NM_001008212
dbSNP: rs2234968
Type: single nucleotide variant
Location: chr10:13109224 (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-thr34 (accessed [today's date]).

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