Is GUCY2D p.Val53= (c.159G>A) pathogenic?

GUCY2D p.Val53= (c.159G>A) is classified Likely benign in GUCY2D (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). No allele count reported in gnomAD v4.1 (AN 1,520,774); Associated with Leber congenital amaurosis 1.

What condition is associated with GUCY2D p.Val53= (c.159G>A)?

GUCY2D p.Val53= (c.159G>A) is associated with Leber congenital amaurosis 1, cone-rod dystrophy 6 (ClinVar).

How common is GUCY2D p.Val53= (c.159G>A) in the general population?

GUCY2D p.Val53= (c.159G>A) is no allele count reported in gnomAD v4.1 (AN 1,520,774) (gnomAD).

How is Leber congenital amaurosis inherited?

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

GUCY2D p.Val53=

c.159G>A · rs2545417437 · VCV2941930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,520,774)

Conditions

Leber congenital amaurosis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.006	GERP -2.1, phastCons 0.002
Overall
CADD	2.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,520,774). 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: GUCY2D
Protein: p.Val53=
Coding: c.159G>A
MANE Select: NM_000180
dbSNP: rs2545417437
Type: single nucleotide variant
Location: chr17:8003206 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.37

Full GUCY2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy 6

For Leber congenital amaurosis (Orphanet):

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

Similar variants

GUCY2D c.1956+1G>A Pathogenic ★★★ same condition
GUCY2D c.3224+1G>C Pathogenic ★★★ same condition
GUCY2D c.3224+3G>T Likely pathogenic ★★★ same condition
GUCY2D p.Ala946Thr Likely pathogenic ★★★ same condition
GUCY2D p.Arg1091Ter Pathogenic ★★★ same condition
GUCY2D p.Arg313Cys Likely pathogenic ★★★ ⚠ same condition
GUCY2D p.Arg521Ter Pathogenic ★★★ same condition
GUCY2D p.Arg588Trp 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/gucy2d-p-val53 (accessed [today's date]).

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