Is CRB1 p.Val1209fs (c.3626_3627del) pathogenic?

CRB1 p.Val1209fs (c.36263627del) is classified Pathogenic in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-24). Absent from gnomAD; Associated with Leber congenital amaurosis.

What condition is associated with CRB1 p.Val1209fs (c.3626_3627del)?

CRB1 p.Val1209fs (c.3626_3627del) is associated with Leber congenital amaurosis (ClinVar).

How common is CRB1 p.Val1209fs (c.3626_3627del) in the general population?

CRB1 p.Val1209fs (c.3626_3627del) is absent from gnomAD (gnomAD).

How is Leber congenital amaurosis inherited?

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

CRB1 p.Val1209fs

c.3626_3627del · rs2528204450 · VCV2577511

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Leber congenital amaurosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.3	GERP 1.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRB1
Protein: p.Val1209fs
Coding: c.3626_3627del
MANE Select: NM_201253
dbSNP: rs2528204450
Type: Microsatellite
Location: chr1:197435486 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 1209: a disulfide bond; a UniProt-annotated variant site (in lca8); the egf-like 16; calcium-binding domain

Full CRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CRB1 p.Val1209Met Uncertain significance ★★ ⚠ same residue
CRB1 p.Asn87Ter Pathogenic ★★ same condition
CRB1 p.Cys221_Glu222delinsTer Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Cys67_Asp68delinsTer Likely pathogenic ★★ same condition
CRB1 p.Glu1276fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Thr1275fs Likely pathogenic ★ same condition
CRB1 c.2129-1G>C Pathogenic ★★ same condition
CRB1 c.2676+1G>A 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-val1209fs (accessed [today's date]).

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