Is OPTN p.His571= (c.1713C>T) pathogenic?

OPTN p.His571= (c.1713C>T) is classified Likely benign in OPTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). Ultra-rare (popmax 0.0557%, eas); Associated with amyotrophic lateral sclerosis type 12.

What condition is associated with OPTN p.His571= (c.1713C>T)?

OPTN p.His571= (c.1713C>T) is associated with amyotrophic lateral sclerosis type 12, OPTN-related open angle glaucoma (ClinVar).

How common is OPTN p.His571= (c.1713C>T) in the general population?

OPTN p.His571= (c.1713C>T) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

OPTN p.His571=

c.1713C>T · rs187326591 · VCV1159109

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Conditions

amyotrophic lateral sclerosis type 12

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 -4	GERP -3.8
Overall
CADD	5.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0557% East Asian · 25/44,896 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00223% 36/1,614,188 alleles · ultra-rare exomes 28/1,461,868 · genomes 8/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,796
African / African-American	0.00666%	15,011
South Asian	0.0022%	45,539
European (non-Finnish)	0.000339%	295,006

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.His571=
Coding: c.1713C>T
MANE Select: NM_001008212
dbSNP: rs187326591
Type: single nucleotide variant
Location: chr10:13136845 (GRCh38)
Gene constraint: LOEUF 0.877 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.90 · 14 PDB
Residue 571: a binding site; an α-helix; the 'interaction with hd' region

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

Disease context

amyotrophic lateral sclerosis type 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: OPTN-related open angle glaucoma

Similar variants

OPTN p.His571Gln Uncertain significance ★ ⚠ same residue
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

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-his571 (accessed [today's date]).

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