Is OPA1 p.Ala550Pro (c.1648G>C) pathogenic?

OPA1 p.Ala550Pro (c.1648G>C) is classified Uncertain significance in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-12). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1; Associated with autosomal dominant optic atrophy, classic form.

What condition is associated with OPA1 p.Ala550Pro (c.1648G>C)?

OPA1 p.Ala550Pro (c.1648G>C) is associated with autosomal dominant optic atrophy, classic form (ClinVar).

How common is OPA1 p.Ala550Pro (c.1648G>C) in the general population?

OPA1 p.Ala550Pro (c.1648G>C) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal dominant optic atrophy, classic form inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about OPA1 p.Ala550Pro (c.1648G>C)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

OPA1 p.Ala550Pro

c.1648G>C · VCV4856384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant optic atrophy, classic form

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic · top 10% in OPA1
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -7.24	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 2.3, phastCons 1
Overall
CADD	33.0	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 A495P vs ClinVar A550P) — 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.Ala550Pro
Coding: c.1648G>C
MANE Select: NM_130837
Type: single nucleotide variant
Location: chr3:193645592 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 495 UniProt numbering: the dynamin-type g domain

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

Disease context

autosomal dominant optic atrophy, classic form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant optic atrophy, classic form (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

OPA1 p.Ala550Asp Likely pathogenic ★ same residue
OPA1 p.Ala550Val Pathogenic ★ ⚠ same residue
OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1149+1G>T Likely pathogenic ★★ same condition
OPA1 c.1230+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1681+1G>T Pathogenic ★★ same condition
OPA1 c.1935+1G>C Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2778+1G>A 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-ala550pro (accessed [today's date]).

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