Is OPA1 p.Arg960Gln (c.2879G>A) pathogenic?

OPA1 p.Arg960Gln (c.2879G>A) is classified Uncertain significance in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-01). AlphaMissense: likely pathogenic (0.6458); Very rare (popmax 0.00137%, afr).

How common is OPA1 p.Arg960Gln (c.2879G>A) in the general population?

OPA1 p.Arg960Gln (c.2879G>A) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about OPA1 p.Arg960Gln (c.2879G>A)?

AlphaMissense predicts likely pathogenic (score 0.6458) — an in-silico prediction, not a clinical call.

OPA1 p.Arg960Gln

c.2879G>A · rs763280368 · VCV809596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6458	likely pathogenic
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R905Q vs ClinVar R960Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,218 alleles

Overall 0.000131% 2/1,529,006 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,218
South Asian	0.00112%	89,402

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.Arg960Gln
Coding: c.2879G>A
MANE Select: NM_130837
dbSNP: rs763280368
Type: single nucleotide variant
Location: chr3:193667176 (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

Similar variants

OPA1 p.Arg960Ter Pathogenic ★★ same residue
OPA1 p.Arg960= Benign/Likely benign ★★ same residue
OPA1 c.1035+1G>A Pathogenic ★★ same type
OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same type
OPA1 c.1149+1G>A Pathogenic ★★ same type
OPA1 c.1149+1G>T Likely pathogenic ★★ same type
OPA1 c.1150-2A>G Pathogenic ★★ same type
OPA1 c.1230+1G>A Pathogenic ★★ same type

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-arg960gln (accessed [today's date]).

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