Is OTX2 p.Val147= (c.441C>G) pathogenic?

OTX2 p.Val147= (c.441C>G) is classified Likely benign in OTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-16). Very rare (popmax 0.00267%, afr); Associated with Anophthalmia-microphthalmia syndrome.

What condition is associated with OTX2 p.Val147= (c.441C>G)?

OTX2 p.Val147= (c.441C>G) is associated with Anophthalmia-microphthalmia syndrome (ClinVar).

How common is OTX2 p.Val147= (c.441C>G) in the general population?

OTX2 p.Val147= (c.441C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

OTX2 p.Val147=

c.441C>G · rs1018175216 · VCV2149193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 7.5	GERP 2.5, phastCons 1
Overall
CADD	10.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,046 alleles · very rare exomes 0/1,461,880 · genomes 2/152,166 · 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.Val147=
Coding: c.441C>G
MANE Select: NM_021728
dbSNP: rs1018175216
Type: single nucleotide variant
Location: chr14:56802188 (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.Val147Ala Uncertain significance ★ ⚠ same residue
OTX2 p.Val147Ile Uncertain significance ★ ⚠ same residue
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

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-val147 (accessed [today's date]).

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