Is CRB1 p.Pro701= (c.2103C>G) pathogenic?

CRB1 p.Pro701= (c.2103C>G) is classified Conflicting classifications of pathogenicity in CRB1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-25). Rare (popmax 0.19%, nfe); Associated with pigmented paravenous retinochoroidal atrophy.

What condition is associated with CRB1 p.Pro701= (c.2103C>G)?

CRB1 p.Pro701= (c.2103C>G) is associated with pigmented paravenous retinochoroidal atrophy, retinitis pigmentosa 12, Leber congenital amaurosis 8 (ClinVar).

How common is CRB1 p.Pro701= (c.2103C>G) in the general population?

CRB1 p.Pro701= (c.2103C>G) is rare (popmax 0.19%, nfe) (gnomAD).

How is Pigmented paravenous retinochoroidal atrophy inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CRB1 p.Pro701=

c.2103C>G · rs144436610 · VCV289997

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.19%, nfe)

Conditions

pigmented paravenous retinochoroidal atrophy

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 -1.6	GERP -1.9
Overall
CADD	1.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.19% European (non-Finnish) · 2,245/1,180,028 alleles

Filtering AF 0.184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.181%

Overall 0.16% 2,583/1,614,096 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.439%	228
European (non-Finnish)grpmax	0.19%	526
Remaining individualsnot grpmax-eligible	0.158%	631
Middle Eastern	0.115%	866
African / African-American	0.0386%	2,588
South Asian	0.0373%	2,679
Admixed American	0.035%	2,858
Finnishnot grpmax-eligible	0.0282%	3,552

Ashkenazi Jewish 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.Pro701=
Coding: c.2103C>G
MANE Select: NM_201253
dbSNP: rs144436610
Type: single nucleotide variant
Location: chr1:197421931 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 701: a UniProt-annotated variant site (in lca8); the egf-like 12 domain; a disulfide bond

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

Disease context

pigmented paravenous retinochoroidal atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 12 Leber congenital amaurosis 8 Leber congenital amaurosis retinitis pigmentosa

For Pigmented paravenous retinochoroidal atrophy (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: All ages

Similar variants

CRB1 p.Pro701fs Likely pathogenic ★ 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.2676+1G>T 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-pro701 (accessed [today's date]).

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