Is OPA1 p.Phe119fs (c.357del) pathogenic?

OPA1 p.Phe119fs (c.357del) is classified Pathogenic in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-22). Very rare (popmax 0.000173%, nfe); Associated with autosomal dominant optic atrophy, classic form.

What condition is associated with OPA1 p.Phe119fs (c.357del)?

OPA1 p.Phe119fs (c.357del) is associated with autosomal dominant optic atrophy, classic form (ClinVar).

How common is OPA1 p.Phe119fs (c.357del) in the general population?

OPA1 p.Phe119fs (c.357del) is very rare (popmax 0.000173%, nfe) (gnomAD).

How is Autosomal dominant optic atrophy, classic form inherited?

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

OPA1 p.Phe119fs

c.357del · rs1728905695 · VCV1526127

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000173%, nfe)

Conditions

autosomal dominant optic atrophy, classic form

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000173% European (non-Finnish) · 2/1,153,868 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,585,212 alleles · very rare exomes 2/1,433,026 · genomes 0/152,186 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OPA1
Protein: p.Phe119fs
Coding: c.357del
MANE Select: NM_130837
dbSNP: rs1728905695
Type: Deletion
Location: chr3:193615676 (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

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 c.2012+4_2012+7del Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2873_2876del Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Gln714fs Likely pathogenic ★★ same condition
OPA1 p.Lys267fs Pathogenic ★★ same condition
OPA1 p.Phe772fs Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Phe802fs Pathogenic ★★ same condition
OPA1 p.Ser763fs Pathogenic ★★ same condition
OPA1 p.Val997fs 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-phe119fs (accessed [today's date]).

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