Is OPA1 p.Ala862Pro (c.2584G>C) pathogenic?

OPA1 p.Ala862Pro (c.2584G>C) is classified Uncertain significance in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-18). AlphaMissense: ambiguous (0.3653); Absent from gnomAD v4.1; Associated with OPA1-related optic atrophy.

What condition is associated with OPA1 p.Ala862Pro (c.2584G>C)?

OPA1 p.Ala862Pro (c.2584G>C) is associated with OPA1-related optic atrophy (ClinVar).

How common is OPA1 p.Ala862Pro (c.2584G>C) in the general population?

OPA1 p.Ala862Pro (c.2584G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPA1 p.Ala862Pro (c.2584G>C)?

AlphaMissense predicts ambiguous (score 0.3653) — an in-silico prediction, not a clinical call.

OPA1 p.Ala862Pro

c.2584G>C · VCV4882120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

OPA1-related optic atrophy

Computational evidence

Protein change
AlphaMissense	0.3653	ambiguous
REVEL	0.467	indeterminate
SaProt	LLR -5.33	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	25.7	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 A807P vs ClinVar A862P) — 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.Ala862Pro
Coding: c.2584G>C
MANE Select: NM_130837
Type: single nucleotide variant
Location: chr3:193662885 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 862: a disulfide bond

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

Disease context

OPA1-related optic atrophy

Similar variants

OPA1 c.1149+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.2012+1G>T Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2178+1G>A Pathogenic ★★ same condition
OPA1 c.2661+1G>T Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2661+2T>C 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-ala862pro (accessed [today's date]).

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