Is OTX2 p.Arg50Ser (c.150G>C) pathogenic?

OTX2 p.Arg50Ser (c.150G>C) is classified Likely pathogenic in OTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-30). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with syndromic microphthalmia type 5.

What condition is associated with OTX2 p.Arg50Ser (c.150G>C)?

OTX2 p.Arg50Ser (c.150G>C) is associated with syndromic microphthalmia type 5 (ClinVar).

How common is OTX2 p.Arg50Ser (c.150G>C) in the general population?

OTX2 p.Arg50Ser (c.150G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OTX2 p.Arg50Ser (c.150G>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

OTX2 p.Arg50Ser

c.150G>C · rs1246931412 · VCV3062100

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic microphthalmia type 5

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar · top 9% in OTX2
REVEL	0.909	moderately pathogenic-leaning
SaProt	LLR -15.37	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 1.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 2,031 bp · p 1.4e-09 · regional, not allelic
Overall
CADD	27.1	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 R42S vs ClinVar R50S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OTX2
Protein: p.Arg50Ser
Coding: c.150G>C
MANE Select: NM_021728
dbSNP: rs1246931412
Type: single nucleotide variant
Location: chr14:56804311 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 50: a DNA-binding region

Full OTX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

syndromic microphthalmia type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OTX2 p.Arg50= Conflicting classifications of pathogenicity ★ same residue
OTX2 p.Glu87Lys Pathogenic/Likely pathogenic ★★ same condition
OTX2 p.Tyr197Ter Pathogenic/Likely pathogenic ★★ same condition
OTX2 p.Arg127Leu Uncertain significance ★★ same condition
OTX2 p.Arg48Trp Uncertain significance ★★ ⚠ same condition
OTX2 p.His238Leu Uncertain significance ★★ ⚠ same condition
OTX2 c.97+12C>T Benign/Likely benign ★★ same condition
OTX2 c.*10G>A Benign/Likely benign ★★ 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/otx2-p-arg50ser (accessed [today's date]).

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