Is OTX2 p.Pro32= (c.96G>T) pathogenic?

OTX2 p.Pro32= (c.96G>T) is classified Uncertain significance in OTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with pituitary hormone deficiency, combined, 6.

What condition is associated with OTX2 p.Pro32= (c.96G>T)?

OTX2 p.Pro32= (c.96G>T) is associated with pituitary hormone deficiency, combined, 6, syndromic microphthalmia type 5 (ClinVar).

How common is OTX2 p.Pro32= (c.96G>T) in the general population?

OTX2 p.Pro32= (c.96G>T) is absent from gnomAD v4.1 (gnomAD).

OTX2 p.Pro32=

Q: How is Combined pituitary hormone deficiencies, genetic forms inherited?

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

c.96G>T · rs1892046623 · VCV880601

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pituitary hormone deficiency, combined, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -4.7
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

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.Pro32=
Coding: c.96G>T
MANE Select: NM_021728
dbSNP: rs1892046623
Type: single nucleotide variant
Location: chr14:56805361 (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

Disease context

pituitary hormone deficiency, combined, 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: syndromic microphthalmia type 5

For Combined pituitary hormone deficiencies, genetic forms (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

OTX2 p.Pro32Thr Uncertain significance ★★ ⚠ same residue
OTX2 p.Pro32Ala Uncertain significance ★ ⚠ same residue
OTX2 p.Pro32Leu Uncertain significance ★ 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

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-pro32 (accessed [today's date]).

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