Is OPA3 p.Val67Phe (c.199G>T) pathogenic?

OPA3 p.Val67Phe (c.199G>T) is classified Uncertain significance in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-03). AlphaMissense: likely benign (0.1867); No allele count reported in gnomAD v4.1 (AN 1,612,028); Associated with OPA3-related disorder.

What condition is associated with OPA3 p.Val67Phe (c.199G>T)?

OPA3 p.Val67Phe (c.199G>T) is associated with OPA3-related disorder (ClinVar).

How common is OPA3 p.Val67Phe (c.199G>T) in the general population?

OPA3 p.Val67Phe (c.199G>T) is no allele count reported in gnomAD v4.1 (AN 1,612,028) (gnomAD).

What do computational predictors say about OPA3 p.Val67Phe (c.199G>T)?

AlphaMissense predicts likely benign (score 0.1867) — an in-silico prediction, not a clinical call.

OPA3 p.Val67Phe

c.199G>T · rs1431669356 · VCV2635410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1867 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,028)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

OPA3-related disorder

Computational evidence

Protein change
AlphaMissense	0.1867	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.69	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.19 · regional, not allelic
Overall
CADD	19.19	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,028). 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: OPA3
Protein: p.Val67Phe
Coding: c.199G>T
MANE Select: NM_025136
dbSNP: rs1431669356
Type: single nucleotide variant
Location: chr19:45553855 (GRCh38)
Gene constraint: LOEUF 1.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.13

Full OPA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

OPA3-related disorder

Similar variants

OPA3 p.Val67Ile Uncertain significance ★ ⚠ same residue
OPA3 p.Val67= Likely benign ★ same residue
OPA3 c.142+1G>A Likely pathogenic ★★ same condition
OPA3 p.Gln105Glu Pathogenic ★★ ⚠ same condition
OPA3 p.Ile41Met Conflicting classifications of pathogenicity ★ ⚠ same condition
OPA3 p.Tyr101Cys Uncertain significance ★ same condition
OPA3 p.Leu133Arg Uncertain significance ⚠ same condition
OPA3 p.Leu129= Likely benign 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/opa3-p-val67phe (accessed [today's date]).

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