Is OTX2 p.Val90= (c.270G>A) pathogenic?

OTX2 p.Val90= (c.270G>A) is classified Likely benign in OTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-11). Very rare (popmax 0.000254%, nfe); Associated with Anophthalmia-microphthalmia syndrome.

What condition is associated with OTX2 p.Val90= (c.270G>A)?

OTX2 p.Val90= (c.270G>A) is associated with Anophthalmia-microphthalmia syndrome (ClinVar).

How common is OTX2 p.Val90= (c.270G>A) in the general population?

OTX2 p.Val90= (c.270G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

OTX2 p.Val90=

c.270G>A · rs747916036 · VCV2734269

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.071	GERP -5.3, phastCons 0.59
Overall
CADD	10.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,036 alleles

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

Overall 0.000186% 3/1,614,058 alleles · very rare exomes 2/1,461,872 · genomes 1/152,186 · joint denominator

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.Val90=
Coding: c.270G>A
MANE Select: NM_021728
dbSNP: rs747916036
Type: single nucleotide variant
Location: chr14:56804191 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 90: a DNA-binding region; a UniProt-annotated variant site (in mcops5; does not affect the expression or nuclear localization of the protein but inhibits its dna-binding activity as well as its transactivation capability; the protein is non-functional)

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-val90 (accessed [today's date]).

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