Is OPA1 p.Val660fs (c.1979_1980del) pathogenic?

OPA1 p.Val660fs (c.19791980del) is classified Pathogenic in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). No gnomAD frequency available for this variant.

How common is OPA1 p.Val660fs (c.1979_1980del) in the general population?

OPA1 p.Val660fs (c.1979_1980del) is no gnomAD frequency available for this variant (gnomAD).

OPA1 p.Val660fs

c.1979_1980del · rs2109083888 · VCV1451913

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 21 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.2, 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.Val660fs
Coding: c.1979_1980del
MANE Select: NM_130837
dbSNP: rs2109083888
Type: Deletion
Location: chr3:193648838 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 660: the 'stalk region' region

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

Similar variants

OPA1 c.1377_1377+4del Pathogenic/Likely pathogenic ★★ same type
OPA1 c.2012+4_2012+7del Pathogenic/Likely pathogenic ★★ same type
OPA1 c.2873_2876del Pathogenic/Likely pathogenic ★★ same type
OPA1 c.2885_2983+8del Pathogenic/Likely pathogenic ★★ same type
OPA1 c.2984-1_2986del Pathogenic/Likely pathogenic ★★ same type
OPA1 p.Asp266fs Pathogenic ★★ same type
OPA1 p.Gln714fs Likely pathogenic ★★ same type
OPA1 p.His686fs 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-val660fs (accessed [today's date]).

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