Is OPA1 p.Ser107= (c.321G>A) pathogenic?

OPA1 p.Ser107= (c.321G>A) is classified Benign in OPA1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.31%, sas); Associated with Behr syndrome.

How common is OPA1 p.Ser107= (c.321G>A) in the general population?

OPA1 p.Ser107= (c.321G>A) is low-frequency (popmax 2.31%, sas) (gnomAD).

OPA1 p.Ser107=

Q: What condition is associated with OPA1 p.Ser107= (c.321G>A)?

OPA1 p.Ser107= (c.321G>A) is associated with Behr syndrome, optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy, autosomal dominant optic atrophy, classic form (ClinVar).

c.321G>A · rs117888848 · VCV95724

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.31%, sas)

Conditions

Behr syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.105	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -3.4, phastCons 0.99
Overall
CADD	7.697	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.31% South Asian · 2,104/91,072 alleles

Filtering AF 2.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.19%

Overall 0.397% 6,414/1,614,114 alleles · low-frequency exomes 5,977/1,461,824 · genomes 437/152,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.31%	43
East Asian	2.28%	44
Middle Eastern	1.45%	69
Ashkenazi Jewishnot grpmax-eligible	0.662%	151
Remaining individualsnot grpmax-eligible	0.448%	223
European (non-Finnish)	0.21%	477
Admixed American	0.198%	504
Finnishnot grpmax-eligible	0.166%	604
African / African-American	0.0306%	3,263

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: OPA1
Protein: p.Ser107=
Coding: c.321G>A
MANE Select: NM_130837
dbSNP: rs117888848
Type: single nucleotide variant
Location: chr3:193615011 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB

Full OPA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Behr syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy autosomal dominant optic atrophy, classic form mitochondrial DNA depletion syndrome 14B (cardioencephalomyopathic type)

Similar variants

OPA1 p.Ser107Leu Uncertain significance ★★ same residue
OPA1 p.Ser107Ter Pathogenic ★ same residue
OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1149+1G>T Likely pathogenic ★★ same condition
OPA1 c.1230+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1681+1G>T Pathogenic ★★ same condition
OPA1 c.1935+1G>C Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1935+1G>T Likely pathogenic ★★ 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/opa1-p-ser107 (accessed [today's date]).

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