CRB1 p.Asp1338=
c.4014T>C · rs778204458 · VCV1582857
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Leber congenital amaurosis 8
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.7 | GERP -3.7 |
| Overall | ||
| CADD | 1.594 | 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
- CRB1
- Protein
- p.Asp1338=
- Coding
- c.4014T>C
- MANE Select
- NM_201253
- dbSNP
- rs778204458
- Type
- single nucleotide variant
- Location
- chr1:197477672 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.19 · 1 PDB
- Residue 1338
- a UniProt-annotated variant site (in lca8)
Disease context
Leber congenital amaurosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: retinitis pigmentosa 12
For Leber congenital amaurosis (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- CRB1 p.Asp1338Glu Uncertain significance ★★ ⚠ same residue
- CRB1 c.1172-2A>G Likely pathogenic ★★ same condition
- CRB1 c.2128+1G>C Pathogenic/Likely pathogenic ★★ same condition
- CRB1 c.2129-1G>A Pathogenic/Likely pathogenic ★★ same condition
- CRB1 c.2129-1G>C Pathogenic ★★ same condition
- CRB1 c.2129-2A>G Pathogenic ★★ same condition
- CRB1 c.2676+1G>A Likely pathogenic ★★ same condition
- CRB1 c.2842+5G>A Pathogenic/Likely pathogenic ★★ 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/crb1-p-asp1338 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown