Is OPA3 p.Ser144= (c.432G>T) pathogenic?

OPA3 p.Ser144= (c.432G>T) is classified Likely benign in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 0.00271%, nfe).

How common is OPA3 p.Ser144= (c.432G>T) in the general population?

OPA3 p.Ser144= (c.432G>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

OPA3 p.Ser144=

c.432G>T · VCV4942869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00271%, 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 -6.8	GERP -3.2
Overall
CADD	0.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,476 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00205% 33/1,609,672 alleles · very rare exomes 31/1,457,480 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,859
Remaining individualsnot grpmax-eligible	0.0016%	62,398

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.Ser144=
Coding: c.432G>T
MANE Select: NM_025136 · reported on NM_001017989
Type: single nucleotide variant
Location: chr19:45529167 (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.Pro144Arg Uncertain significance ★★ ⚠ same residue
OPA3 p.Pro144Gln Uncertain significance ★ ⚠ same residue
OPA3 p.Pro144Thr Uncertain significance ★ same residue
OPA3 p.Pro144fs 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

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-ser144 (accessed [today's date]).

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