Is CRX p.Pro263= (c.789C>T) pathogenic?

CRX p.Pro263= (c.789C>T) is classified Likely benign in CRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 0.00667%, amr); Associated with cone-rod dystrophy 2.

What condition is associated with CRX p.Pro263= (c.789C>T)?

CRX p.Pro263= (c.789C>T) is associated with cone-rod dystrophy 2, Leber congenital amaurosis 7 (ClinVar).

How common is CRX p.Pro263= (c.789C>T) in the general population?

CRX p.Pro263= (c.789C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

How is Cone rod dystrophy inherited?

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

CRX p.Pro263=

c.789C>T · rs550083287 · VCV1604259

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

cone-rod dystrophy 2

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 -11	GERP -3.4
Overall
CADD	1.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,002 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00211% 34/1,614,138 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
African / African-American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00446%	22,432
South Asian	0.0022%	45,544
European (non-Finnish)	0.00153%	65,558

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: CRX
Protein: p.Pro263=
Coding: c.789C>T
MANE Select: NM_000554
dbSNP: rs550083287
Type: single nucleotide variant
Location: chr19:47839856 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI 0.72 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 61.78 · 1 PDB

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

Disease context

cone-rod dystrophy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leber congenital amaurosis 7

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CRX c.101-1G>A Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg40Gln Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg40Trp Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg41Gln Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg43Cys Pathogenic ★★ same condition
CRX p.Arg43His Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg69Cys Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg69His 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/crx-p-pro263 (accessed [today's date]).

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