Is CRB1 p.Ser797Pro (c.2389T>C) pathogenic?

CRB1 p.Ser797Pro (c.2389T>C) is classified Conflicting classifications of pathogenicity in CRB1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-21). AlphaMissense: likely pathogenic (0.7802); Absent from gnomAD v4.1; Associated with Leber congenital amaurosis 8.

What condition is associated with CRB1 p.Ser797Pro (c.2389T>C)?

CRB1 p.Ser797Pro (c.2389T>C) is associated with Leber congenital amaurosis 8 (ClinVar).

How common is CRB1 p.Ser797Pro (c.2389T>C) in the general population?

CRB1 p.Ser797Pro (c.2389T>C) is absent from gnomAD v4.1 (gnomAD).

How is Leber congenital amaurosis inherited?

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

What do computational predictors say about CRB1 p.Ser797Pro (c.2389T>C)?

AlphaMissense predicts likely pathogenic (score 0.7802) — an in-silico prediction, not a clinical call.

CRB1 p.Ser797Pro

c.2389T>C · rs1355198242 · VCV522783

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7802 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,962)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Leber congenital amaurosis 8

Computational evidence

Protein change
AlphaMissense	0.7802	likely pathogenic · top 9% in CRB1
REVEL	0.537	indeterminate
SaProt	LLR -12.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3.1, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 209 kb · p 0.78 · regional, not allelic
Overall
CADD	19.06	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,962). 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.Ser797Pro
Coding: c.2389T>C
MANE Select: NM_201253
dbSNP: rs1355198242
Type: single nucleotide variant
Location: chr1:197427714 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 797: 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

For Leber congenital amaurosis (Orphanet):

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

Similar variants

CRB1 p.Ser797= Likely benign ★ 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-ser797pro (accessed [today's date]).

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