Is OPA1 p.Arg5His (c.14G>A) pathogenic?

OPA1 p.Arg5His (c.14G>A) is classified Uncertain significance in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-16). AlphaMissense: ambiguous (0.3787); No allele count reported in gnomAD v4.1 (AN 1,547,878).

How common is OPA1 p.Arg5His (c.14G>A) in the general population?

OPA1 p.Arg5His (c.14G>A) is no allele count reported in gnomAD v4.1 (AN 1,547,878) (gnomAD).

What do computational predictors say about OPA1 p.Arg5His (c.14G>A)?

AlphaMissense predicts ambiguous (score 0.3787) — an in-silico prediction, not a clinical call.

OPA1 p.Arg5His

c.14G>A · VCV3338716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3787 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,547,878)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3787	ambiguous
REVEL	0.164	moderately benign-leaning
SaProt	LLR -8.09	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.16, phastCons 0.81
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,547,878). 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.Arg5His
Coding: c.14G>A
MANE Select: NM_130837
Type: single nucleotide variant
Location: chr3:193593391 (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

Similar variants

OPA1 c.1035+1G>A Pathogenic ★★ same type
OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same type
OPA1 c.1149+1G>A Pathogenic ★★ same type
OPA1 c.1149+1G>T Likely pathogenic ★★ same type
OPA1 c.1150-2A>G Pathogenic ★★ same type
OPA1 c.1230+1G>A Pathogenic ★★ same type
OPA1 c.1230+5G>A Pathogenic/Likely pathogenic ★★ same type
OPA1 c.1305+1G>T 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/opa1-p-arg5his (accessed [today's date]).

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