Is CRB1 p.Phe786= (c.2358T>C) pathogenic?

CRB1 p.Phe786= (c.2358T>C) is classified Likely benign in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). Very rare (popmax 0.000339%, nfe); Associated with Leber congenital amaurosis 8.

What condition is associated with CRB1 p.Phe786= (c.2358T>C)?

CRB1 p.Phe786= (c.2358T>C) is associated with Leber congenital amaurosis 8, retinitis pigmentosa 12 (ClinVar).

How common is CRB1 p.Phe786= (c.2358T>C) in the general population?

CRB1 p.Phe786= (c.2358T>C) is very rare (popmax 0.000339%, nfe) (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.Phe786=

c.2358T>C · rs1371610654 · VCV793244

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Leber congenital amaurosis 8

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 -0.49	GERP -0.99
Overall
CADD	1.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,940 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,954 alleles · very rare exomes 5/1,461,636 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)grpmax	0.000339%	294,985

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRB1
Protein: p.Phe786=
Coding: c.2358T>C
MANE Select: NM_201253
dbSNP: rs1371610654
Type: single nucleotide variant
Location: chr1:197427683 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 786: a UniProt-annotated variant site (in lca8); the laminin g-like 2 domain

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 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
CRB1 c.2843-1G>T 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-phe786 (accessed [today's date]).

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