Is CRX p.Tyr258= (c.774T>C) pathogenic?

CRX p.Tyr258= (c.774T>C) is classified Likely benign in CRX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-20). Ultra-rare (popmax 0.0362%, sas); Associated with Leber congenital amaurosis 7.

What condition is associated with CRX p.Tyr258= (c.774T>C)?

CRX p.Tyr258= (c.774T>C) is associated with Leber congenital amaurosis 7, cone-rod dystrophy 2 (ClinVar).

How common is CRX p.Tyr258= (c.774T>C) in the general population?

CRX p.Tyr258= (c.774T>C) is ultra-rare (popmax 0.0362%, sas) (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.Tyr258=

c.774T>C · rs767273026 · VCV1674290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

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 -10	GERP -3.4
Overall
CADD	0.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% South Asian · 33/91,094 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00223% 36/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0048%	20,827

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.Tyr258=
Coding: c.774T>C
MANE Select: NM_000554
dbSNP: rs767273026
Type: single nucleotide variant
Location: chr19:47839841 (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

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.Tyr258Ter Likely pathogenic ★ same residue
CRX p.Tyr258Cys Uncertain significance ★ ⚠ 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
CRX p.Arg41Gln Pathogenic/Likely pathogenic ★★ same condition
CRX p.Arg43Cys Pathogenic ★★ same condition
CRX p.Arg43His 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-tyr258 (accessed [today's date]).

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