Is OPA1 p.Arg810Pro (c.2429G>C) pathogenic?

OPA1 p.Arg810Pro (c.2429G>C) is classified Uncertain significance in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1.

How common is OPA1 p.Arg810Pro (c.2429G>C) in the general population?

OPA1 p.Arg810Pro (c.2429G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPA1 p.Arg810Pro (c.2429G>C)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

OPA1 p.Arg810Pro

c.2429G>C · VCV3658732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic · top 7% in OPA1
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -7.65	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 2.4, phastCons 1
Overall
CADD	32.0	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 R755P vs ClinVar R810P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OPA1
Protein: p.Arg810Pro
Coding: c.2429G>C
MANE Select: NM_130837
Type: single nucleotide variant
Location: chr3:193658984 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 755 UniProt numbering: the 'stalk region' region; the 'paddle region' region

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

Similar variants

OPA1 p.Arg810His Uncertain significance ★★ ⚠ same residue
OPA1 p.Arg810Cys Uncertain significance ★ ⚠ 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-arg810pro (accessed [today's date]).

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