Is OTX2 p.Pro27= (c.81C>T) pathogenic?

OTX2 p.Pro27= (c.81C>T) is classified Likely benign in OTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-04). Very rare (popmax 0.000254%, nfe); Associated with Anophthalmia-microphthalmia syndrome.

What condition is associated with OTX2 p.Pro27= (c.81C>T)?

OTX2 p.Pro27= (c.81C>T) is associated with Anophthalmia-microphthalmia syndrome (ClinVar).

How common is OTX2 p.Pro27= (c.81C>T) in the general population?

OTX2 p.Pro27= (c.81C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

OTX2 p.Pro27=

c.81C>T · rs1892047371 · VCV1626309

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Anophthalmia-microphthalmia syndrome

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 0.46	GERP -3, phastCons 0.98
Overall
CADD	7.802	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,178,832 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,524 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OTX2
Protein: p.Pro27=
Coding: c.81C>T
MANE Select: NM_021728
dbSNP: rs1892047371
Type: single nucleotide variant
Location: chr14:56805376 (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

Anophthalmia-microphthalmia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OTX2 p.Arg76Ter Pathogenic ★★ same condition
OTX2 p.Ser211Ter Pathogenic/Likely pathogenic ★★ same condition
OTX2 p.Ala234Val Uncertain significance ★★ ⚠ same condition
OTX2 p.Arg102His Uncertain significance ★★ ⚠ same condition
OTX2 p.Arg48Trp Uncertain significance ★★ ⚠ same condition
OTX2 p.Leu64Met Uncertain significance ★★ ⚠ same condition
OTX2 p.Lys95Glu Uncertain significance ★★ ⚠ same condition
OTX2 p.Pro141Thr 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-pro27 (accessed [today's date]).

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