Is OPA3 p.Pro173= (c.519A>T) pathogenic?

OPA3 p.Pro173= (c.519A>T) is classified Likely benign in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). Ultra-rare (popmax 0.0206%, nfe).

How common is OPA3 p.Pro173= (c.519A>T) in the general population?

OPA3 p.Pro173= (c.519A>T) is ultra-rare (popmax 0.0206%, nfe) (gnomAD).

OPA3 p.Pro173=

c.519A>T · VCV4942865

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0206%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.68	GERP -1.7
Overall
CADD	2.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0206% European (non-Finnish) · 241/1,172,324 alleles

Filtering AF 0.0184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0175%

Overall 0.0158% 253/1,600,354 alleles · ultra-rare exomes 234/1,448,444 · genomes 19/151,910 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0206%	4,864
Finnishnot grpmax-eligible	0.0096%	10,413
Remaining individualsnot grpmax-eligible	0.00485%	20,600
African / African-American	0.00403%	24,843

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OPA3
Protein: p.Pro173=
Coding: c.519A>T
MANE Select: NM_025136 · reported on NM_001017989
Type: single nucleotide variant
Location: chr19:45529080 (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.Ala173= Likely benign ★★ same residue
OPA3 p.Ala173Thr Uncertain significance ★ ⚠ same residue
OPA3 p.Pro173Arg 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

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-pro173 (accessed [today's date]).

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