Is OPA1 p.Ser324Pro (c.970T>C) pathogenic?

OPA1 p.Ser324Pro (c.970T>C) is classified Likely pathogenic in OPA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-01). AlphaMissense: likely pathogenic (0.9989); No allele count reported in gnomAD v4.1 (AN 1,599,210); Associated with optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy.

How common is OPA1 p.Ser324Pro (c.970T>C) in the general population?

OPA1 p.Ser324Pro (c.970T>C) is no allele count reported in gnomAD v4.1 (AN 1,599,210) (gnomAD).

How is Autosomal dominant optic atrophy plus syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about OPA1 p.Ser324Pro (c.970T>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

OPA1 p.Ser324Pro

Q: What condition is associated with OPA1 p.Ser324Pro (c.970T>C)?

OPA1 p.Ser324Pro (c.970T>C) is associated with optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy (ClinVar).

c.970T>C · rs2109011385 · VCV1185094

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,210)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic ✓ concordant with ClinVar · top 4% in OPA1
REVEL	0.943	strongly pathogenic-leaning
SaProt	LLR -14.63	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S269P vs ClinVar S324P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,599,210). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OPA1
Protein: p.Ser324Pro
Coding: c.970T>C
MANE Select: NM_130837
dbSNP: rs2109011385
Type: single nucleotide variant
Location: chr3:193637216 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 269 UniProt numbering: an α-helix

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

Disease context

optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant optic atrophy plus syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

OPA1 c.1149+1G>T Likely pathogenic ★★ same condition
OPA1 c.556+1G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Arg345Gln Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Arg500His Pathogenic/Likely pathogenic ★★ ⚠ same condition
OPA1 p.Arg912Ter Pathogenic ★★ same condition
OPA1 p.Asp351Glu Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Asp493Gly Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Gly494Val 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-ser324pro (accessed [today's date]).

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