Is OTX2 p.Pro32Ala (c.94C>G) pathogenic?

OTX2 p.Pro32Ala (c.94C>G) is classified Uncertain significance in OTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). AlphaMissense: likely benign (0.075); Absent from gnomAD v4.1.

How common is OTX2 p.Pro32Ala (c.94C>G) in the general population?

OTX2 p.Pro32Ala (c.94C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OTX2 p.Pro32Ala (c.94C>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

OTX2 p.Pro32Ala

c.94C>G · rs2139537137 · VCV1696963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.516	indeterminate
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 1,128 bp · p 0.31 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

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.Pro32Ala
Coding: c.94C>G
MANE Select: NM_021728
dbSNP: rs2139537137
Type: single nucleotide variant
Location: chr14:56805363 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.99

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

Similar variants

OTX2 p.Pro32Thr Uncertain significance ★★ ⚠ same residue
OTX2 p.Pro32= Uncertain significance ★ same residue
OTX2 p.Pro32Leu Uncertain significance ★ same residue
OTX2 p.Arg76Ter Pathogenic ★★ same type
OTX2 p.Glu87Lys Pathogenic/Likely pathogenic ★★ same type
OTX2 p.Ser211Ter Pathogenic/Likely pathogenic ★★ same type
OTX2 p.Tyr197Ter Pathogenic/Likely pathogenic ★★ same type
OTX2 p.Ala234Val Uncertain significance ★★ ⚠ 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/otx2-p-pro32ala (accessed [today's date]).

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