Is CRX c.*400A>T pathogenic?

CRX c.400A>T is classified Benign in CRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Common (popmax 39.2%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Leber congenital amaurosis 7.

What condition is associated with CRX c.*400A>T?

CRX c.*400A>T is associated with Leber congenital amaurosis 7, cone-rod dystrophy 2, retinitis pigmentosa (ClinVar).

How is Leber congenital amaurosis inherited?

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

CRX c.*400A>T

Q: How common is CRX c.*400A>T in the general population?

CRX c.*400A>T is common (popmax 39.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs3848536 · VCV329708

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 39.2%, nfe) — too common for a highly-penetrant pathogenic allele

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 0.16	GERP -1.3, phastCons 0.002
Overall
CADD	1.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.2% European (non-Finnish) · 42,424/108,270 alleles

Filtering AF 38.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.7%

Overall 33.1% 72,569/219,220 alleles · common exomes 23,160/67,498 · genomes 49,409/151,722 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	47.2%	2
European (non-Finnish)grpmax	39.2%	3
Ashkenazi Jewishnot grpmax-eligible	33.8%	3
Admixed American	33%	3
Finnishnot grpmax-eligible	32.9%	3
Remaining individualsnot grpmax-eligible	32.9%	3
Middle Eastern	32.8%	3
South Asian	31.7%	3
African / African-American	22.1%	5
East Asian	13.2%	8

Amish 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: CRX
Coding: c.*400A>T
MANE Select: NM_000554
dbSNP: rs3848536
Type: single nucleotide variant
Location: chr19:47840367 (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 retinitis pigmentosa

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
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-c-star-400a-t (accessed [today's date]).

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