Is OPA1 p.Arg71Pro (c.212G>C) pathogenic?

OPA1 p.Arg71Pro (c.212G>C) is classified Uncertain significance in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.1855); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with OPA1 p.Arg71Pro (c.212G>C)?

OPA1 p.Arg71Pro (c.212G>C) is associated with Inborn genetic diseases (ClinVar).

How common is OPA1 p.Arg71Pro (c.212G>C) in the general population?

OPA1 p.Arg71Pro (c.212G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPA1 p.Arg71Pro (c.212G>C)?

AlphaMissense predicts likely benign (score 0.1855) — an in-silico prediction, not a clinical call.

OPA1 p.Arg71Pro

c.212G>C · rs766106312 · VCV2547870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1855	likely benign
REVEL	0.593	indeterminate
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP 1.1, phastCons 0.29
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

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.Arg71Pro
Coding: c.212G>C
MANE Select: NM_130837
dbSNP: rs766106312
Type: single nucleotide variant
Location: chr3:193614902 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OPA1 p.Arg71Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
OPA1 p.Arg71Gly Uncertain significance ★ ⚠ same residue
OPA1 p.Arg71His Conflicting classifications of pathogenicity ★ ⚠ same residue
OPA1 p.Arg71= Likely benign ★ same residue
OPA1 c.1608+5G>A Uncertain significance ★★ same condition
OPA1 p.Ala364Val Uncertain significance ★★ ⚠ same condition
OPA1 p.Ala758Val Uncertain significance ★★ ⚠ same condition
OPA1 p.Arg216Cys Uncertain significance ★★ ⚠ 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-arg71pro (accessed [today's date]).

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