Is CRX p.Ser199fs (c.591_594dup) pathogenic?

CRX p.Ser199fs (c.591594dup) is classified Pathogenic in CRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). Absent from gnomAD; Associated with Leber congenital amaurosis 7.

What condition is associated with CRX p.Ser199fs (c.591_594dup)?

CRX p.Ser199fs (c.591_594dup) is associated with Leber congenital amaurosis 7, cone-rod dystrophy 2 (ClinVar).

How common is CRX p.Ser199fs (c.591_594dup) in the general population?

CRX p.Ser199fs (c.591_594dup) is absent from gnomAD (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.Ser199fs

c.591_594dup · rs2514256327 · VCV2017828

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Leber congenital amaurosis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.15	GERP -1.8, phastCons 0.46

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRX
Protein: p.Ser199fs
Coding: c.591_594dup
MANE Select: NM_000554
dbSNP: rs2514256327
Type: Duplication
Location: chr19:47839655 (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.Ser199= Conflicting classifications of pathogenicity ★ same residue
CRX p.Thr155fs Likely pathogenic ★★ same condition
CRX p.Tyr191fs Pathogenic ★★ same condition
CRX p.Asp140fs Pathogenic ★ same condition
CRX p.Gly183fs Likely pathogenic ★ same condition
CRX p.Pro184fs Pathogenic ★ same condition
CRX p.Pro244fs Pathogenic ★ same condition
CRX p.Ser185fs 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-ser199fs (accessed [today's date]).

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