Is CRB1 p.Ser371Pro (c.1110_1111delinsGC) pathogenic?

CRB1 p.Ser371Pro (c.11101111delinsGC) is classified Uncertain significance in CRB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-11). Absent from gnomAD; Associated with retinitis pigmentosa 12.

What condition is associated with CRB1 p.Ser371Pro (c.1110_1111delinsGC)?

CRB1 p.Ser371Pro (c.1110_1111delinsGC) is associated with retinitis pigmentosa 12, pigmented paravenous retinochoroidal atrophy, Leber congenital amaurosis 8 (ClinVar).

How common is CRB1 p.Ser371Pro (c.1110_1111delinsGC) in the general population?

CRB1 p.Ser371Pro (c.1110_1111delinsGC) is absent from gnomAD (gnomAD).

How is Retinitis pigmentosa inherited?

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

CRB1 p.Ser371Pro

c.1110_1111delinsGC · rs1660514556 · VCV866126

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

retinitis pigmentosa 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.6
Regional constraint	o/e 1.01	unconstrained · MANE · 209 kb · p 0.78 · regional, not allelic

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.Ser371Pro
Coding: c.1110_1111delinsGC
MANE Select: NM_201253
dbSNP: rs1660514556
Type: Indel
Location: chr1:197356952 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 371: the egf-like 9 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

retinitis pigmentosa 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pigmented paravenous retinochoroidal atrophy Leber congenital amaurosis 8

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CRB1 c.2842+1delinsAA Pathogenic ★★ same condition
CRB1 p.Arg92fs Pathogenic ★ same condition
CRB1 p.Gln1004_Asp1005delinsHisPhe Pathogenic ★ same condition
CRB1 p.Gly929fs Likely pathogenic ★ same condition
CRB1 p.Ser545fs Likely pathogenic ★ same condition
CRB1 p.Thr1207fs Likely pathogenic ★ same condition
CRB1 p.Thr431fs Likely pathogenic ★ same condition
CRB1 p.Tyr1019fs 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-ser371pro (accessed [today's date]).

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