Is OPA3 p.Pro173Arg (c.518C>G) pathogenic?

OPA3 p.Pro173Arg (c.518C>G) is classified Uncertain significance in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). Very rare (popmax 0.00443%, sas).

How common is OPA3 p.Pro173Arg (c.518C>G) in the general population?

OPA3 p.Pro173Arg (c.518C>G) is very rare (popmax 0.00443%, sas) (gnomAD).

OPA3 p.Pro173Arg

c.518C>G · VCV4942866

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00443%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.199	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -2
Overall
CADD	0.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00443% South Asian · 4/90,208 alleles

Filtering AF 0.00144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000898%

Overall 0.0005% 8/1,600,744 alleles · very rare exomes 6/1,448,644 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00443%	22,552
African / African-American	0.00268%	37,280
Admixed American	0.00169%	59,096
Remaining individualsnot grpmax-eligible	0.00162%	61,776

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.Pro173Arg
Coding: c.518C>G
MANE Select: NM_025136 · reported on NM_001017989
Type: single nucleotide variant
Location: chr19:45529081 (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.Pro173= Likely benign ★ 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-pro173arg (accessed [today's date]).

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