Is OPA1 p.Arg960Ter (c.2878C>T) pathogenic?

OPA1 p.Arg960Ter (c.2878C>T) is classified Pathogenic in OPA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-07). Very rare (popmax 0.000275%, nfe); Associated with OPA1-related disorder.

What condition is associated with OPA1 p.Arg960Ter (c.2878C>T)?

OPA1 p.Arg960Ter (c.2878C>T) is associated with OPA1-related disorder, optic atrophy (ClinVar).

How common is OPA1 p.Arg960Ter (c.2878C>T) in the general population?

OPA1 p.Arg960Ter (c.2878C>T) is very rare (popmax 0.000275%, nfe) (gnomAD).

OPA1 p.Arg960Ter

c.2878C>T · VCV3250035

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000275%, nfe)

Conditions

OPA1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 29 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.5, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000275% European (non-Finnish) · 3/1,090,686 alleles

Filtering AF 7.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.00022% 3/1,363,944 alleles · very rare

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.Arg960Ter
Coding: c.2878C>T
MANE Select: NM_130837
Type: single nucleotide variant
Location: chr3:193667175 (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

OPA1-related disorder

Also linked: optic atrophy

Similar variants

OPA1 p.Arg960= Benign/Likely benign ★★ same residue
OPA1 p.Arg960Gln Uncertain significance ★ ⚠ same residue
OPA1 c.1149+1G>A Pathogenic ★★ same condition
OPA1 c.1230+1G>A Pathogenic ★★ same condition
OPA1 c.1230+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1305+1G>T Pathogenic ★★ same condition
OPA1 c.1377+1G>A Pathogenic ★★ same condition
OPA1 c.1935+1G>C 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-arg960ter (accessed [today's date]).

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