Is OPA3 p.Ile91Phe (c.271A>T) pathogenic?

OPA3 p.Ile91Phe (c.271A>T) is classified Uncertain significance in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.1386); Absent from gnomAD v4.1.

How common is OPA3 p.Ile91Phe (c.271A>T) in the general population?

OPA3 p.Ile91Phe (c.271A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OPA3 p.Ile91Phe (c.271A>T)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

OPA3 p.Ile91Phe

c.271A>T · VCV4942891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.5	GERP -3.3
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.19 · regional, not allelic
Overall
CADD	15.21	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

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: OPA3
Protein: p.Ile91Phe
Coding: c.271A>T
MANE Select: NM_025136
Type: single nucleotide variant
Location: chr19:45553783 (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

Similar variants

OPA3 p.Ile91= Likely benign ★★ same residue
OPA3 p.Ile91Met Uncertain significance ★ ⚠ same residue
OPA3 c.142+1G>A Likely pathogenic ★★ same type
OPA3 c.143-1G>A Pathogenic ★★ same type
OPA3 c.143-1G>C Pathogenic ★★ same type
OPA3 p.Gln105Glu Pathogenic ★★ ⚠ same type
OPA3 p.Met1Val Likely pathogenic ★★ same type
OPA3 c.142+4A>T Uncertain significance ★★ 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/opa3-p-ile91phe (accessed [today's date]).

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