Is CRX p.Glu80= (c.240G>A) pathogenic?

CRX p.Glu80= (c.240G>A) is classified Likely benign in CRX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). Ultra-rare (popmax 0.0165%, mid); Associated with Leber congenital amaurosis 7.

What condition is associated with CRX p.Glu80= (c.240G>A)?

CRX p.Glu80= (c.240G>A) is associated with Leber congenital amaurosis 7, cone-rod dystrophy 2 (ClinVar).

How common is CRX p.Glu80= (c.240G>A) in the general population?

CRX p.Glu80= (c.240G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Leber congenital amaurosis inherited?

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

CRX p.Glu80=

c.240G>A · rs1968118313 · VCV1934900

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Leber congenital amaurosis 7

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 1.9	GERP 0.82, phastCons 1
Overall
CADD	7.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000205% 3/1,461,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,036

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.Glu80=
Coding: c.240G>A
MANE Select: NM_000554
dbSNP: rs1968118313
Type: single nucleotide variant
Location: chr19:47836382 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI 0.72 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 61.78 · 1 PDB
Residue 80: a DNA-binding region; an α-helix; a UniProt-annotated variant site (in cord2)

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

Disease context

Leber congenital amaurosis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy 2

For Leber congenital amaurosis (Orphanet):

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

Similar variants

CRX p.Glu80Ala Pathogenic ★★ same residue
CRX p.Glu80Lys Pathogenic ★★ same residue
CRX p.Glu80Gln Likely pathogenic ★ same residue
CRX p.Glu80Gly Pathogenic ★ same residue
CRX p.Glu80Val Likely pathogenic ★ same residue
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

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-glu80 (accessed [today's date]).

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