Is CRB1 p.Asp397= (c.1191C>T) pathogenic?

CRB1 p.Asp397= (c.1191C>T) is classified Likely benign in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-03). Ultra-rare (popmax 0.011%, sas); Associated with retinitis pigmentosa 12.

What condition is associated with CRB1 p.Asp397= (c.1191C>T)?

CRB1 p.Asp397= (c.1191C>T) is associated with retinitis pigmentosa 12, Leber congenital amaurosis 8 (ClinVar).

How common is CRB1 p.Asp397= (c.1191C>T) in the general population?

CRB1 p.Asp397= (c.1191C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

CRB1 p.Asp397=

c.1191C>T · rs758897056 · VCV1146547

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP 1.1, phastCons 0.011
Overall
CADD	12.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/90,838 alleles

Filtering AF 0.00595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00454%

Overall 0.00145% 21/1,449,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,084
East Asian	0.00669%	14,944
Remaining individualsnot grpmax-eligible	0.00161%	62,040
European (non-Finnish)	0.000599%	167,004

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.Asp397=
Coding: c.1191C>T
MANE Select: NM_201253
dbSNP: rs758897056
Type: single nucleotide variant
Location: chr1:197421019 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 397: a UniProt-annotated variant site (in lca8); the egf-like 10; calcium-binding domain

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: 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 p.Asp397His 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-asp397 (accessed [today's date]).

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