Is CRB1 p.Pro329fs (c.986del) pathogenic?

CRB1 p.Pro329fs (c.986del) is classified Pathogenic in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-08). Absent from gnomAD; Associated with Leber congenital amaurosis 8.

What condition is associated with CRB1 p.Pro329fs (c.986del)?

CRB1 p.Pro329fs (c.986del) is associated with Leber congenital amaurosis 8, retinitis pigmentosa 12 (ClinVar).

How common is CRB1 p.Pro329fs (c.986del) in the general population?

CRB1 p.Pro329fs (c.986del) 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.Pro329fs

c.986del · rs2527647307 · VCV2034662

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 8

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 4 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.2	GERP 0.61, 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.Pro329fs
Coding: c.986del
MANE Select: NM_201253
dbSNP: rs2527647307
Type: Deletion
Location: chr1:197347476 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 329: the egf-like 8 domain; a UniProt-annotated variant site (in lca8); a disulfide bond

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

Disease context

Leber congenital amaurosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also 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.Pro329= Uncertain significance ★ same residue
CRB1 c.652+3_652+6del Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Ala1374fs Pathogenic ★★ same condition
CRB1 p.Asn7fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Asp1299fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Asp47fs Pathogenic ★★ same condition
CRB1 p.Cys1143fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Cys1148fs 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-pro329fs (accessed [today's date]).

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