Is OPA1 p.Phe1007Ter (c.3013_3019dup) pathogenic?

OPA1 p.Phe1007Ter (c.30133019dup) is classified Conflicting classifications of pathogenicity in OPA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-06-06). No gnomAD frequency available for this variant; Associated with OPA1-related disorder.

What condition is associated with OPA1 p.Phe1007Ter (c.3013_3019dup)?

OPA1 p.Phe1007Ter (c.3013_3019dup) is associated with OPA1-related disorder (ClinVar).

How common is OPA1 p.Phe1007Ter (c.3013_3019dup) in the general population?

OPA1 p.Phe1007Ter (c.3013_3019dup) is no gnomAD frequency available for this variant (gnomAD).

OPA1 p.Phe1007Ter

c.3013_3019dup · rs1553797598 · VCV447903

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

OPA1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (30 of 31, 44 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP 0.86, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OPA1
Protein: p.Phe1007Ter
Coding: c.3013_3019dup
MANE Select: NM_130837
dbSNP: rs1553797598
Type: Duplication
Location: chr3:193692088 (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

OPA1-related disorder

Similar variants

OPA1 p.Asp170Ter Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Gly464fs Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Ser387fs Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Asn636Ter Likely pathogenic ★ same condition
OPA1 p.Asp525fs Likely pathogenic ★ same condition
OPA1 p.Gln1001fs Likely pathogenic ★ same condition
OPA1 p.His513fs Pathogenic ★ same condition
OPA1 p.Ile818fs 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-phe1007ter (accessed [today's date]).

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