Is OPA1 p.Ile751= (c.2253A>T) pathogenic?

OPA1 p.Ile751= (c.2253A>T) is classified Likely benign in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-06). Absent from gnomAD v4.1.

How common is OPA1 p.Ile751= (c.2253A>T) in the general population?

OPA1 p.Ile751= (c.2253A>T) is absent from gnomAD v4.1 (gnomAD).

OPA1 p.Ile751=

c.2253A>T · rs1714052195 · VCV2812400

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.1, phastCons 1
Overall
CADD	10.46	PHRED · no single calibrated threshold — expert panels disagree

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.Ile751=
Coding: c.2253A>T
MANE Select: NM_130837
dbSNP: rs1714052195
Type: single nucleotide variant
Location: chr3:193657154 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 751: 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.Ile751Val Uncertain significance ★★ ⚠ same residue
OPA1 p.Ile751Thr Uncertain significance ★ ⚠ same residue
OPA1 p.Ile751_Phe752insTer Pathogenic ★ 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

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-ile751 (accessed [today's date]).

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