Is OPA1 p.Arg987= (c.2961C>T) pathogenic?

OPA1 p.Arg987= (c.2961C>T) is classified Benign/Likely benign in OPA1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.18%, eas); Associated with autosomal dominant optic atrophy, classic form.

What condition is associated with OPA1 p.Arg987= (c.2961C>T)?

OPA1 p.Arg987= (c.2961C>T) is associated with autosomal dominant optic atrophy, classic form (ClinVar).

How common is OPA1 p.Arg987= (c.2961C>T) in the general population?

OPA1 p.Arg987= (c.2961C>T) is low-frequency (popmax 2.18%, eas) (gnomAD).

How is Autosomal dominant optic atrophy, classic form inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

OPA1 p.Arg987=

c.2961C>T · rs35540805 · VCV95723

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.18%, eas)

Conditions

autosomal dominant optic atrophy, classic form

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.131	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -5.3
Overall
CADD	4.552	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.18% East Asian · 975/44,726 alleles

Filtering AF 2.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.02%

Overall 0.254% 4,030/1,586,394 alleles · low-frequency exomes 2,900/1,434,154 · genomes 1,130/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.18%	46
African / African-American	2.13%	47
South Asian	0.867%	115
Remaining individualsnot grpmax-eligible	0.388%	257
Ashkenazi Jewishnot grpmax-eligible	0.329%	304
Admixed American	0.325%	308
Middle Eastern	0.25%	400
European (non-Finnish)	0.0119%	8,368

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: OPA1
Protein: p.Arg987=
Coding: c.2961C>T
MANE Select: NM_130837
dbSNP: rs35540805
Type: single nucleotide variant
Location: chr3:193667258 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB

Full OPA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant optic atrophy, classic form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant optic atrophy, classic form (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

OPA1 p.Arg987Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
OPA1 p.Arg987His Conflicting classifications of pathogenicity ★ ⚠ same residue
OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1149+1G>T Likely pathogenic ★★ same condition
OPA1 c.1230+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1681+1G>T Pathogenic ★★ same condition
OPA1 c.1935+1G>C Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2778+1G>A 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/opa1-p-arg987 (accessed [today's date]).

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