Is CRX p.Ser19Arg (c.57T>A) pathogenic?

CRX p.Ser19Arg (c.57T>A) is classified Uncertain significance in CRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely pathogenic (0.8478); Absent from gnomAD v4.1; Associated with cone-rod dystrophy 2.

What condition is associated with CRX p.Ser19Arg (c.57T>A)?

CRX p.Ser19Arg (c.57T>A) is associated with cone-rod dystrophy 2, Leber congenital amaurosis 7 (ClinVar).

How common is CRX p.Ser19Arg (c.57T>A) in the general population?

CRX p.Ser19Arg (c.57T>A) is absent from gnomAD v4.1 (gnomAD).

How is Cone rod dystrophy inherited?

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

What do computational predictors say about CRX p.Ser19Arg (c.57T>A)?

AlphaMissense predicts likely pathogenic (score 0.8478) — an in-silico prediction, not a clinical call.

CRX p.Ser19Arg

c.57T>A · VCV3749821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cone-rod dystrophy 2

Computational evidence

Protein change
AlphaMissense	0.8478	likely pathogenic
REVEL	0.271	benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.3
Regional constraint	o/e 0.89	unconstrained · MANE · 1,933 bp · p 0.26 · regional, not allelic
Overall
CADD	14.32	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRX
Protein: p.Ser19Arg
Coding: c.57T>A
MANE Select: NM_000554
Type: single nucleotide variant
Location: chr19:47834500 (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-ser19arg (accessed [today's date]).

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