Is OPA1 p.Val347Phe (c.1039G>T) pathogenic?

OPA1 p.Val347Phe (c.1039G>T) is classified Likely pathogenic in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely pathogenic (0.9865); Absent from gnomAD v4.1.

How common is OPA1 p.Val347Phe (c.1039G>T) in the general population?

OPA1 p.Val347Phe (c.1039G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPA1 p.Val347Phe (c.1039G>T)?

AlphaMissense predicts likely pathogenic (score 0.9865) — an in-silico prediction, not a clinical call.

OPA1 p.Val347Phe

c.1039G>T · rs2109014867 · VCV1398078

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9865	likely pathogenic ✓ concordant with ClinVar
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -15.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2, phastCons 1
Overall
CADD	29.3	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 V292F vs ClinVar V347F) — 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.Val347Phe
Coding: c.1039G>T
MANE Select: NM_130837
dbSNP: rs2109014867
Type: single nucleotide variant
Location: chr3:193637955 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 347: the dynamin-type g domain

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

Similar variants

OPA1 p.Val347Gly Uncertain significance ★ ⚠ 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
OPA1 c.1230+1G>A Pathogenic ★★ same type
OPA1 c.1230+5G>A Pathogenic/Likely 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-val347phe (accessed [today's date]).

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